4,5-diaryl-3(2H)-furanone derivatives as cyclooxygenase-2 inhibitors

ABSTRACT

The present invention provides a novel class of 4,5-diaryl-3(2H)-furanone derivatives, which inhibit strongly and selectively COX-2 over COX-1. They are useful to treat inflammation, inflammation-associated disorders, and COX-2 mediated diseases.

This application is a 371 of PCT/KR00/00339 filed Apr. 12, 2000, now WO00/61571 Oct. 19, 2000.

FIELD OF INVENTION

The present invention relates generally to 4,5-diaryl-3(2H)-furanonederivatives, methods of preparation therefor, and their use for thetreatment of inflammation and inflammation-associated disorders asselective cyclooxygenase-2 inhibitors.

BACKGROUND OF THE INVENTION

Prostaglandins are known to play an important roles in the inflammation.Since prostaglandins are produced from arachidonic acid bycyclooxygenases, inhibition of prostagalndin synthesis bycyclooxygenases, especially synthesis of PGE₂, PGG₂, and PGH₂, leads tothe treatment of inflammation.

There are at least two kinds of cyclooxygenases, cyclooxygenase-1(abbreviated as COX-1) and cyclooxygenase-2 (abbreviated as COX-2).COX-1 is constitutively present in the gastrointestinal tract and thekidney, and is implicated to be responsible for the maintenance of thephysiological homeostasis, such as gastrointestinal integrity and renalfunction. Interruption of COX-1 activity can lead to life-threateningtoxicities to the gastrointestinal tract, such as ulceration andbleeding. In the meantime, COX-2 is induced upon inflammatory stimuliand known to be responsible for progression of inflammation. Thus,selective inhibition of COX-2 over COX-1 is useful for the treatment ofinflammation and inflammation-associated disorders without incurringgastrointestinal toxicities.

Conventional non-steroidal anti-inflammatory drugs (NSAIDs), such asindomethacin, naproxen, ketoprofen, ibuprofen, piroxicam, diclofenacetc, inhibit both COX-1 and COX-2, which would demonstrate theirgastrointestinal toxicities as well as anti-inflammatory potency.However, they possess serious life-threatening gastrointestinaltoxicities of bleeding and ulceration arising from their inhibition ofCOX-1, which limit their clinical use. Thus, a selective inhibitor ofCOX-2 can be useful as an anti-inflammatory therapeutic agent withoutthe gastrointestinal toxicities, frequently occurring upon chronic useof conventional NSAIDs.

COX-2 inhibitors are implicated to possess a broad therapeutic spectrumbesides anti-inflammatory, analgesic, and antipyretic activity. Forexample inhibition of COX-2 can prevent growth of certain types ofcancer, especially colon cancer [J. Clin. Invest. 99, 2254 (1997)].Another application of a COX-2 inhibitor can be found in the treatmentof degenerative chronic neurological disorders, such as Alzheimer'sdisease [Neurology 48, 626 (1997)]. COX-2 inhibition would be useful inreducing the infarct volume accompanying the stroke [J. Neuroscience 17,2746 (1997)].

Recently two of COX-2 selective antiinflammatory drugs, celecoxib androfecoxib, were introduced into the clinic for arthritic indications.Celecoxib and rofecoxib show anti-inflammatory potency comparable toconventional NSAIDs without COX-2 selectivity. In the meantime, thesedrugs show appreciably lower gastro-intestinal toxicities thanconventional NSAIDs without COX-2 selectivity over COX-1. Thus, COX-2selective inhibition itself can be enough for anti-arthritic potency andthe inhibition of COX-1 is largely responsible for the gastrointestinaltoxicities associated with conventional NSAIDs without COX-2selectivity.

cis-1,2-Diaryl-alkenes or its structural-equivalents are known to be apharmacophore for achieving selective COX-2 inhibition over COX-1 [Ann.Rep. Med. Chem. 32, 211 (1997)]. In case of celecoxib and rofecoxib,pyrazole and 2(5H)-furanone correspond to the scaffold, respectively.

By adopting an appropriate scaffold for the cis-alkene pharmacophore, itwould be possible to modulate both in vitro and in vivo characteristicsof such inhibitors, such as dosing regimen, daily dose, clinicalindications arising from tissue distribution characteristics, safetyprofile, and so on.

In this invention, 3(2H)-furanone is adopted as a scaffold for COX-2inhibitors. 3(2H)-furanone derivatives were prepared for use in thetreatment of glaucoma [EP 0 737 476 A2]. However, there is no precedentcase that 3(2H)-furanone derivatives have been ever used as COX-2inhibitors. There is no reported case of 4,5-diaryl-3(2H)-furanonederivatives, either.

The 4,5-diaryl-3(2H)-furanone derivatives disclosed herein selectivelyinhibit COX-2 over COX-1 and relieve the effects of inflammation.4,5-Diaryl-3(2H)-furanone derivatives of this invention do not showsubstantial inhibition of COX-1 and consequently show reducedgastrointestinal side effects. Thus, 4,5-diaryl-3(2H)-furanonederivatives of this invention are found useful as anti-inflammatoryagents with significantly reduced gastrointestinal side effects, whencompared with conventional NSAIDs.

SUMMARY OF INVENTION

The present invention provides a novel class of potent selective COX-2inhibitors.

The present invention provides a novel class of 3(2H)-furanonederivatives as selective COX-2 inhibitors, which are represented byFormula I:

or a pharmaceutically-acceptable salt thereof, wherein:

X represents halo, hydrido, or alkyl;

Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)-sulfonyl, (N-alkylamino)sulfonyl, or alkylthio;

Z represents oxygen or sulfur atom;

R₁ and R₂ are selected independently from lower alkyl radicals, or forma 4- to 6-membered aliphatic or hetero cyclic group, taken together withthe 2-position carbon atom of the 3(2H)-furanone ring;

and AR represents a substituted or non-substituted aromatic group of 5to 10 atoms.

The present invention further provides methods for preparing3(2H)-furanone derivatives of Formula I.

BRIEF DISCRIPTION THE DRAWINGS

FIG. 1 is a graph showing pharmacokinetics for orally administeredExample 393 at 10 mg/kg body weight.

DESCRIPTION OF INVENTION

A novel class of 4,5-diaryl-3(2H)-furanone derivatives useful intreating inflammation and inflammation-associated disorders is definedby Formula I:

or a pharmaceutically-acceptable salt thereof, wherein:

X represents halo, hydrido, or alkyl;

Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)-sulfonyl, (N-alkylamino)sulfonyl, or alkylthio;

Z represents oxygen or sulfur atom;

R₁ and R₂ are selected independently from lower alkyl radicals, or forma 4- to 6-membered aliphatic or hetero cyclic group, taken together withthe 2-position carbon atom of 3(2H)-furanone ring;

and AR represents a substituted or non-substituted aromatic group of 5to 10 atoms.

4,5-diaryl-3(2H)-furanone derivatives of this invention selectivelyinhibit COX-2 over COX-1, and thus can be useful for the treatment ofinflammation and inflammation-associated disorders but with reducedgastrointestinal toxicities when compared with conventional NSAIDs.

Compounds of Formula I would be useful for, but not limited to, therelief of inflammation, pain and fever. For example, compounds ofFormula I would be useful to treat inflammation and pain from arthritis,including but not limited to rheumatoid arthritis, spondyloarthopathies,gout, oesteoarthritis, systemic lupus erythematosus and juvenilearthritis. Compounds of Formula I would be useful for the relief of painassociated with, including but not limited to, headache, toothache,dysmenorrhea, neuralgia, and bodily pain such as in the neck and in thelow back. Compounds of Formula I would be useful to relieve symptomsassociated with common cold, viral infections including but not limitedto influenza. Compounds of Formula I would be useful for the treatmentof inflammatory conditions, including but not limited to, myositis,gingivitis, synovitis, ankylosing spondylitis, burstitis, burns, injury,and so on. Compounds of Formula I would be useful in the relief ofinflammation and pain after surgical and dental operation. Suchcompounds are useful to treat psoriasis, eczema, and dermatitis.Compounds of Formula I would be useful for the treatment of inflammatoryconditions associated with, including but not limited to, inflammatorybowel disease, Crohn's disease, type I diabetes, and the like. Suchcompounds may be useful to inhibit cyclooxygenase-mediated growth ofcertain types of cancer, including but not limited to colon cancer.Compounds of Formula I would be useful to reduce the infarct volume ofreperfusion injury following stroke. Such compounds would be useful toalleviate inflammatory conditions in, including but not limited to,asthma and bronchitis. Compounds of Formula I would be useful in thetreatment of degenerative neurological disorders including Alzheimer'sdisease. Such compounds would be useful in the treatment of retinopathyassociated with diabetes, which involves cyclooxygenase-mediatedangiogenesis.

Considering their high COX-2 selectivity over COX-1, compounds ofFormula I would show significantly reduced gastrointestinal side effectssuch as ulceration and bleeding, when compared with conventional NSAIDs.Thus, compounds of Formula I may be useful as a far safer alternative toconventional NSAIDs. Compounds of Formula I may be useful in thetreatment of humans as well as animals, including but not limited to,cattle, sheep, dogs, horses, and the like.

Compounds of Formula I may be used with other anti-inflammatories,including but not limited to, steroids, conventional NSAIDs such asaspirin, acetaminophen, diclofenac, indomethacin, ibuprofen, and thelike. Compounds of Formula I can be used with a variety of therapeutics,including but not limited to, a H₂-antagonist, an anti-hypertensiveincluding but not limited to an ACE inhibitor, a prostaglandin, ananti-histamine, an immuno-modulator including methotrexate, ananti-coagulant, and the like.

Compounds of Formula I can be administered by various methods, includingbut not limited to, oral, intravenous, subcutaneous, topicaladministration, and the like. Compounds of Formula I can be administeredalong with various pharmaceutically-acceptable adjuvant ingredients,including but not limited to, citric acid, hydrochloric acid, sodiumchloride, tartaric acid, stearic acid, starch, gelatin, talc, sesameoil, ascorbic acid, olive oil, palm oil, methylcellulose, sodiumcarboxymethylcelluose, polyethyleneglycol (PEG), polypropyleneglycol,sweeteners, preservatives, ethanol, titanium oxide, sodium bicarbonate,soybean lecithin, and the like. Compounds of Formula I can be formulatedin a variety of dosage forms, including but not limited to, tablet,powder, granule, hard capsule, soft capsule, oral suspension, spraysolution for inhalation, injectable solution, and the like.

A compound of Formula I can be converted into thepharmaceutically-acceptable salt by neutralizing the compound, dependingon the presence of an acidic group or a basic group in the compound,with an equivalent amount of an appropriate pharmaceutically-acceptableacid or base, such as potassium hydroxide, sodium hydroxide,hydrochloric acid, methansulfonic acid, citric acid, and the like.

Compounds of Formula I can be administered to humans at daily doses of0.1 to 100 mg/kg body weight depending on indications, symptoms, orcondition of a patient. Preferred daily doses of the compound of FormulaI, however, may be between 0.1 and 10 mg/kg bodyweight for inflammatoryindications such as rheumatoid arthritis. Compounds of Formula I can beadministered according to various schedules, including but not limitedto, daily once, daily twice, three times a day, and the like.

A preferred class of compounds encompasses those compounds of Formula I,wherein X is selected from halo, hydrido and lower alkyl; wherein Y isselected from (lower alkyl)sulfonyl, aminosulfonyl, (loweralkyl)sulfinyl, (lower N-acylamino)-sulfonyl, (lowerN-alkylamino)sulfonyl and (lower alkyl)thio; wherein Z is selected fromoxygen and sulfur atom; wherein R₁ and R₂ are selected independentlyfrom lower alkyl radicals, or R₁ and R₂ represent pentylidenyl(—CH₂—CH₂—CH₂—CH₂—), hexylidenyl (—CH₂—CH₂—CH₂—CH₂—CH₂—),4-tetrahydro-(4H)-pyranylidenyl (—CH₂—CH₂—O—CH₂—CH₂—),3-tetrahydrofuranylidenyl (—CH₂—O—CH₂—CH₂—) or 3-oxetanylidenyl(—CH₂—O—CH₂—) to form a cycle taken together with the 2-position carbonatom of the 3(2H)-furanone ring; and wherein AR represents a substitutedor non-substituted aromatic group of 5 to 10 atoms, which is selectedfrom, but not limited to, the aromatic groups encompassing

wherein, each of R₃ to R₇, if present, is independently selected fromhydrido, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino,N-alkylamino, N,N-dialkylamino, N-acylamino, (haloacyl)amino, formyl,cyano, azido, hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl andhydroxyalkyl, or adjacent two groups of R₃ to R₇ form, taken together,methylenedioxy; and wherein each of R₈ to R₁₉, if present, is selectedfrom hydrido, halo, alkyl, acyl, haloalkyl, alkoxy, formyl, cyano,nitro, amino, azido and N-acylamino; or a pharmaceutically-acceptablesalt thereof.

A class of compounds of particular interest encompasses those compoundsof Formula I, wherein X is selected from fluoro, chloro, bromo, hydrido,methyl, ethyl, and n-propyl; wherein Y is selected from methylsulfonyl,ethylsulfonyl, n-propylsulfonyl, aminosulfonyl, methylsulfonyl,ethylsulfonyl, n-propylsulfonyl, (N-acetylamino)sulfonyl,(N-propionylamino)sulfonyl, (N-butyrylamino)sulfonyl,(N-methylamino)sulfonyl, (N-ethylamino)sulfonyl, methylthio, ethylthio,and n-propylthio; wherein Z is selected from oxygen and sulfur atom;wherein R₁ and R₂ are selected independently from methyl and ethyl, orR₁ and R₂ represent, taken together, pentylidenyl (—CH₂—CH₂—CH₂—CH₂—),hexylidenyl (—CH₂—CH₂—CH₂—CH₂—CH₂—), 4-tetrahydro-(4H)-pyranylidenyl(—CH2—CH₂—O—CH₂—CH₂—), 3-tetrahydrofuranylidenyl (—CH₂—O—CH₂—CH₂—), and3-oxetanylidenyl (—CH₂—O—CH₂—) to form a cycle with the 2-positioncarbon atom of the 3(2H)-furanone ring; wherein each of R₃ to R₇, ifpresent, is independently selected from hydrido, fluoro, chloro, bromo,methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl,n-pentyl, iso-pentyl, fluoromethyl, difluoromethyl, trifluoromethyl,2-fluoroethyl, 1-fluoroethyl, 2,2-difluoroethyl, 1,2-difluoroethyl,1,1-difluoroethyl, 2,2,2-trifluoroethyl, methoxy, ethoxy, n-propyloxy,iso-propyloxy, n-butoxy, trifluoromethoxy, difluoromethoxy,fluoromethoxy, acetyl, propionyl, n-butanoyl, iso-butanoyl, n-pentanoyl,nitro, amino, N-methylamino, N-ethylamino, N-n-propylamino,N,N-dimethylamino, N-acetylamino, N-propionylamino,N-(trifluoroacetyl)amino, formyl, hydroxy, methylthio, ethylthio,n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl,hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl, or adjacent two groupsof R₃ to R₇ form, taken together, methylenedioxy; and wherein each of R₈to R₁₉, if present, is selected from hydrido, fluoro, chloro, bromo,methyl, ethyl, n-propyl, isopropyl, acetyl, propionyl, methoxy, ethoxy,iso-propyloxy, n-propyloxy and formyl; or a pharmaceutically acceptablesalt thereof.

Within Formula I there is a subclass of compounds of high interestrepresented by Formula II:

wherein Y represents alkylsulfonyl, aminosulfonyl, alkylsulfonyl,(N-acylamino)sulfonyl, (N-alkylamino)sulfonyl, or alkylthio; wherein Zrepresents oxygen or sulfur atom; R₁ and R₂ are selected independentlyfrom lower alkyl radicals; and wherein each of R₃ to R₇, if present, isindependently selected from hydrido, halo, alkyl, haloalkyl, alkoxy,haloalkoxy, acyl, nitro, amino, N-alkylamino, N,N-dialkylamino,N-acylamino, N-(haloacyl)amino, formyl, cyano, azido, hydroxy,alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or twoadjacent groups of R₃ and R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.

A preferred class of compounds comprises those compounds of Formula II,wherein Y is selected from (lower alkyl)sulfonyl, aminosulfonyl, (loweralkyl)sulfonyl, (lower N-acylamino)sulfonyl, (lowerN-alkylamino)sulfonyl, and (lower alkyl)thio; wherein Z is selected fromoxygen and sulfur atom; wherein R₁ and R₂ are independently selectedfrom methyl and ethyl radical; and wherein each of R₃ to R₇, if present,is independently selected from hydrido, halo, lower alkyl, lowerhaloalkyl, lower alkoxy, lower haloalkoxy, lower acyl, nitro, amino,lower N-alkylamino, lower N,N-dialkylamino, lower N-acylamino, (lowerhaloacyl)amino, formyl, cyano, azido, hydroxy, lower alkylthio, loweralkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl, or twoadjacent groups of R₃ to R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.

A class of compounds of particular interest encompasses those compoundsof Formula II, wherein Y is selected from methylsulfonyl, aminosulfonyl,methylsulfonyl, (N-acetylamino)sulfonyl, (N-propionylamino)sulfonyl,(N-butyrylamino)sulfonyl, (N-methylamino)sulfonyl,(N-ethylamino)sulfonyl, and methylthio; wherein Z is selected fromoxygen and sulfur atom; wherein R₁ and R₂ are independently selectedfrom methyl and ethyl radical; and wherein each of R₃ to R₇, if present,is independently selected from hydrido, fluoro, chloro, bromo, methyl,ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl,iso-pentyl, fluoromethyl, difluoromethyl, trifluoromethyl,1-fluoroethyl, 2,2,2-trifluoroethyl, methoxy, trifluoromethoxy,difluoromethoxy, fluoromethoxy, acetyl, propionyl, n-butanoyl,iso-butanoyl, n-pentanoyl, nitro, amino, N,N-dimethylamino,N-acetylamino, N-propionylamino, formyl, hydroxy, methylthio, ethylthio,n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl,hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl, or adjacent two groupsof R₃ to R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IIcomprises the compounds and pharmaceutically acceptable salts thereof asfollows:

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-4-(2-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluoro-4-phenylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-5-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Chloro-3-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2,4-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Bromophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Bromophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-ethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-n-propylphenyl)-3(2H)-furanone;

2,2-Dimethyl-4-(3-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone,

2,2-Dimethyl-4-(4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone:

2,2-Dimethyl-4-(3-fluoro-4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-iso-propylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-n-butylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-t-butylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-fluoro-2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluoro-4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2,4-Dimethoxyphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Dimethoxyphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3,4-methylenedioxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3,4-dimethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluoro-4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(methylthio)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(ethylthio)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4,5-di-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(ethylsulfonyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{3-(fluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(fluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-(Difluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{4-(Difluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-Acetyl-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{3,5-di-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{4-Chloro-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-nitrophenyl)-3(2H)-furanone;

4-(3-Aminophenyl)-2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(N,N-dimethylamino)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-(Acetylamino)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Biphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-[4-(1-hydroxyethyl)phenyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-[4-(hydroxymethyl)phenyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3,5-difluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-5-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4(4-t-Butylphenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfinyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-{3-Acetyl-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;

2,2-Dimethyl-4-(4-methoxyphenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3-chloro-5-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,4-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-{3-chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl3(2H)-furanone;

4-{3-Acetyl-5-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl3(2H)-furanone;

4-{4-Acetyl-5-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-methylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,4-dimethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(2,4-dimethoxyphenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,4-dimethoxyphenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(3-Acetyl-5-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(3-Acetyl-4-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(3-Acetyl-4-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(3-Acetyl-5-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-methoxyphenyl)-3(2H)-furanone;

4-(4-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(4-Acetyl-3-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(4-Acetyl-3-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-(4-Acetyl-3-bromophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

4-{4-(Acetylamino)phenyl}-5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-methylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-methylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3,4-methylenedioxy)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(methylthio)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluoro-4-phenylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(4-bromophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-iso-propyl-2-methoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-iso-propylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(ethylthio)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-methoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(4-n-butylphenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,4,5-trimethoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-hydroxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluoro-3-methoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-ethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-phenylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;

4-(3-Aminophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-nitrophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl)}-4-phenyl-3(2H)-furanone;

2-Ethyl-4-(4-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(2-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-3-chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-3-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-5-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(4-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

4-(3-Acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Acetyl-4-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Acetyl-4-chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-(Acetylamino)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-4-{3,4-(methylenedioxy)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{4-Chloro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;

4-{5-Chloro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;

2-Ethyl-4-{5-fluoro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}3(2H)-furanone;

2-Ethyl-4-(4-ethylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-fluoro-4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(5-fluoro-4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-iso-propylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-t-Butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}4-(4-n-propylphenyl)-3(2H)-furanone;

4-(4-n-Butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Dimethylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Aminophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-(Difluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-{4-(fluoromethyl)phenyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethoxy)phenyl}-3(2H)-furanone;

4-(4-Chloro-3-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(4-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(5-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,4-Dimethoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Dimethoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(5-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-fluoro-4-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3,5-Dimethyl-4-methoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3,4,5-trimethoxyphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(4-fluorophenyl)-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-fluorophenyl)-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-methylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3-chlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(4-chlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;

5-(4-Aminosulfonylphenyl)-2-ethyl-2-methyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

5-(4-Aminosulfonylphenyl)-2-ethyl-2-methyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-3(2H)-furanone;

5-(4-Aminosulfonylphenyl)-4-{3-chloro-5-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,5-difluorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(3,4-difluorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-methoxyphenyl)-2-methyl-3(2H)-furanone;

4-(4-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;

4-(4-Acetyl-3-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;

4-(4-Acetyl-3-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;

4-{4-Acetyl-4-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(4-fluoro-3-methoxyphenyl)-2-methyl-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl -3(2H)-furanone;

2,2-Diethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-3-chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-3-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-2-chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-Acetyl-2-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3,4-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3,5-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(2,5-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-5-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3,4-dimethoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-n-propylphenyl)-3(2H)-furanone;

2,2-Diethyl-4-(2,4-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(4-t-Butylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(3,4-dimethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Diethyl-4-(4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3-(2H)-furanone;

2,2-Diethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;

2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;

5-[4-{(Acetylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-[4-{(Butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-[4-{(N-methylamino)sulfonyl}phenyl]-4-(3-fluorophenyl)-3(2,H)-furanone;

2,2-Dimethyl-5-[4-{(N-ethylamino)sulfonyl}phenyl]-4-(3-fluorophenyl)-3(2H)-furanone.

Within Formula I there is a subclass of compounds of high interestrepresented by Formula III:

wherein Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)sulfonyl, (N-alkylamino)sulfonyl, or alkylthio; wherein Zrepresents oxygen or sulfur atom; wherein m and n are integers from 1 to3 inclusive, with proviso that (m+n)≦4; wherein P is selected fromoxygen atom and methylene radical (—CH₂—); and wherein each of R₃ to R₇,if present, is independently selected from hydrido, halo, alkyl,haloalkyl, alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino,N,N-dialkylamino, N-acylamino, N-(haloacyl)amino, formyl, cyano, azido,hydroxy, alkylthio, alkylsulfonyl, phenyl, alkoxyallkyl andhydroxyallkyl, or two adjacent groups of R₃ to R₇, form, taken together,methylenedioxy; or a pharmaceutically-acceptable salt thereof.

A preferred class of compounds comprises those compounds of Formula III;wherein Y is selected from (lower alkyl)sulfonyl, aminosulfonyl, (loweralkyl)sulfinyl, (lower N-acylamino)sulfonyl, (lowerN-alkylamino)sulfonyl, and (lower alkyl)thio; wherein Z is selected fromoxygen and sulfur atom; wherein m and n are integers from 1 to 3inclusive, with proviso that (m+n)≦4; wherein P is selected from oxygenatom and methylene radical (—CH₂—); and wherein each of R₃ to R₇, ifpresent, is independently selected from hydrido, halo, alkyl, haloalkyl,alkoxy, haloalkoxy, acyl, nitro, amino, N-alkylamino, N,N-dialkylamino,N-acylamino, N-(haloacyl)amino, formyl, cyano, azido, hydroxy,alkylthio, alkylsulfonyl, phenyl, lower alkoxyalkyl and lowerhydroxyalkyl, or adjacent two groups of R₃ to R₇ form, taken together,methylenedioxy; or a pharmaceutically acceptable salt thereof.

A class of compounds of particular interest encompasses those compoundsof Formula III, wherein Y is selected from methylsulfonyl,aminosulfonyl, methylsulfinyl, (N-acetylamino)sulfonyl,(N-propionylamino)sulfonyl, (N-butyrylamino)sulfonyl,(N-methylamino)sulfonyl, (N-ethylamino)sulfonyl, and methylthio; whereinZ is selected from oxygen and sulfur atom; wherein m and n are integersfrom 1 to 3 inclusive, with proviso that (m+n)≦4; wherein P is oxygenatom or methylene radical (—CH₂—); and wherein each of R₃ to R₇, ifpresent, is independently selected from hydrido, fluoro, chloro, bromo,methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl,acetyl, and propionyl; or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IIIcomprises compounds and pharmaceutically acceptable salts thereof asfollows:

2-{4-(Methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,4]non-2-en-4-one;

3-(3-Methylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one;

3-(4-iso-Propylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(3,5-Difluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(2-Fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(3-Fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(3-Chlorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(4-Fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(4-Acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(4-Acetyl-3-fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

3-(4-Acetyl-3-chlorophenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-ene-4-one;

2-{4-(Methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,5]dec-2-en-4-one;

2-{4-(Methylsulfonyl)phenyl}-3-{3-(trifluoromethyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one;

3-(3-Methylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one;

3-(4-Acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one;

3-(3-Fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4.5]dec-2-en-4-one;

3-(3,5-difluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4.5]dec-2-en-4-one;

3-(3-Chlorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4.5]dec-2-en-4-one;

3-(4-Acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4.5]dec-2-en-4-one;

2-{4-(Methylsulfonyl)phenyl}-3-phenyl-1,8-dioxa-spiro[4.5]dec-2-en-4-one;

3-(3-Chlorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4.5]dec-2-en-4-one.

Within Formula I there is a subclass of compounds of high interestrepresented by Formula IV:

wherein X represents halo or alkyl; wherein Y represents alkylsulfonyl,aminosulfonyl, alkylsulfonyl, (N-acylamino)sulfonyl,(N-alkylamino)sulfonyl, or alkylthio; wherein Z represents oxygen orsulfur atom; and wherein each of R₃ to R₇, if present, is independentlyselected from hydrido, halo, alkyl, haloalkyl, alkyloxy, nitro, amino,N-acylamino, acyl, formyl, hydroxyalkyl, phenyl, and cyano, or twoadjacent groups of R₃ to R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.

A preferred class of compounds comprises those compounds of Formula IV,wherein X represents halo or lower alkyl; wherein Y is selected from(lower alkyl)sulfonyl, aminosulfonyl, (lower alkyl)sulfinyl, (lowerN-acylamino)sulfonyl, (lower N-alkylamino)sulfonyl, and (loweralkyl)thio; wherein Z is selected from oxygen and sulfur atom; andwherein each of R₃ to R₇, if present, is independently selected fromhydrido, halo, lower alkyl, lower haloalkyl, lower alkyloxy, nitro,amino, and N-(lower acyl)amino; or a pharmaceutically acceptable saltthereof.

A class of compounds of particular interest encompasses those compoundsof Formula IV, wherein X represents fluoro, chloro, bromo or methyl;wherein Y is selected from methylsulfonyl, ethylsulfonyl, aminosulfonyl,methylsulfinyl, ethylsulfinyl, (N-acetylamino)sulfonyl,(N-propionylamino)sulfonyl, (N-butyrylamino)-sulfonyl,(N-methylamino)sulfonyl, (N-ethylamino)sulfonyl, methylthio, andethylthio; wherein Z is selected from oxygen and sulfur atom; andwherein each of R₃ to R₇, if present, is independently selected fromhydrido, fluoro, chloro, bromo, methyl, ethyl, iso-propyl, fluoromethyl,difluoromethyl, trifluoromethyl, methoxy, ethoxy, n-propyloxy,iso-propyloxy, n-butoxy, nitro, amino, N-acetylamino, andN-propionylamino; or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IVcomprises compounds and pharmaceutically acceptable salts thereof asfollows:

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4Aminosulfonyl)-3-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,4-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,6-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(2-trifuoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(4-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(4-nitrophenyl)-3(2H)-furanone;

4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4(4-Aminophenyl)-5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-3(2H)-furanone;

4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)furanone;

4-{4-(Acetylamino)phenyl}-5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-methoxyphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-methoxyphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(2-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(2,4-difluorophenyl)2,2-dimethyl-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluoropheny}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4(methylsulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone:

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-methylphenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{3-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(3chlorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-4(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{2-Chloro-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-methyl-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone

2,2-Dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-5-{3-methyl4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4(methylthio)phenyl}-3(2H)-furanone

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)-3-methylphenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;

5-{3-Chloro-4-(N-methylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

5-{3-Chloro-4-(N-ethylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

5-[4-{(Acetylamino)sulfonyl}-3-chlorophenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-[3-Chloro-4-{(N-n-propionylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;

5-[3-Chloro-4-{(N-n-butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-(2H)-furan-3-thion

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-(2H)-furan-3-thion

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-(2H)-furan-3-thion

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-(2H)-furan-3-thion

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylthio)phenyl}-(2H)-furan-3-thione;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylsulfonyl)phenyl}-(2H)-furan-3-thione;

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylsulfinyl)phenyl}-(2H)-furan-3-thione;

5-{(4-Aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2dimethyl-(2H)-furan-3-thione.

Within Formula I there is a subclass of compounds of high interestrepresented by Formula V:

wherein Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)sulfonyl, (N-alkylamino)sulfonyl, or alkylthio; wherein Zrepresents oxygen or sulfur atom; wherein R₁ and R₂ are independentlyselected from methyl and ethyl radical; and wherein AR is a substitutedor non-substituted aromatic group of 5 to 10 atoms excluding substitutedor non-substituted phenyl group; or a pharmaceutically-acceptable saltthereof.

A preferred class of compounds comprises those compounds of Formula V,wherein Y is selected from (lower alkyl)sulfonyl, aminosulfonyl, and(lower N-acylamino)sulfonyl; wherein Z is selected from oxygen andsulfur atom; wherein R₁ and R₂ are independently selected from methyland ethyl radical; and wherein AR is selected from the followingspecific aromatic groups:

wherein, each of R₈ to R₁₉, if present, is selected from hydrido, halo,lower alkyl, lower acyl, lower haloalkyl, lower alkoxy, formyl, cyano,nitro, amino, azido, and N-acylamino; or a pharmaceutically acceptablesalt thereof.

A class of compounds of particular interest encompasses those compoundsof Formula V, wherein Y is selected from methylsulfonyl, ethylsulfonyl,aminosulfonyl, (N-acetylamino)sulfonyl, and (N-propionylamino)sulfonyl;wherein Z is selected from oxygen and sulfur atom; wherein R₁ and R₂ areindependently selected from methyl and ethyl radical; and wherein eachof R₈ to R₁₉, if present, is selected from hydrido, fluoro, chloro,bromo, methyl, ethyl, iso-propyl, acetyl, n-proionyl, trifluoromethyl,methoxy, ethoxy, and formyl; or a pharmaceutically acceptable saltthereof.

A family of specific compounds of particular interest within Formula Vcomprises compounds and pharmaceutically-acceptable salts thereof asfollows:

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(3-thienyl)-3(2H)-furanone;

2,2-Dimethyl-4-{2-(3-methylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{2-(5-formylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2-Benzo[b]thienyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(1-naphthyl)-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-pyridyl)-3(2H)-furanone;

4-(2-Benzo[b]furanyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4(2-naphthyl)-3(2H)-furanone;

2,2-Dimethyl-4-{5-(2-fluorothienyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{5-(3-fluorothienyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(2-fluorothienyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone;

4-{2-(5-Acetylthienyl)}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(2-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-(3-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{5-(3-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{5-(2-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(2-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(1-N-ethylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyridyl)-3(2H)-furanone;

2,2-Dimethyl-4-{3-(6-methoxypyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{4-(1-N-iso-propylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl)}-4-(5-pyrimidinyl)-3(2H)-furanone;

2,2-Dimethyl-4-{3-(6-methylpyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-{2-(5-formyl-4-methylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-4-[2-{5-(1,3-dioxolan)-2-yl}thienyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{2-(5-Bromothienyl)}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazolyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(2-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(4-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(1-N-methylpyrazolyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(1-N-ethylpyrazolyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-thienyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(2-fluorothienyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(2-fluorothienyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(3-fluorothienyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(2-furanyl)-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-furanyl)-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(3-fluorofuranyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(2-fluorofuranyl)}-2-methyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(2-fluorofuranyl)}-2-methyl-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-pyridyl)-3(2H)-furanone;

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyridyl)-3(2H)-furanone;

2,2-Diethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone;

2-Ethyl-2-methyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazolyl)-3(2H)-furanone;

2-Ethyl-4-{4-(1-N-ethylpyrazolyl)}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;

2-Ethyl-2-methyl-4-{3-(6methoxypyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-4-{3-(6-methylpyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(2-fluorothienyl)}-3(2H)-furanone;

2-Ethyl-4-(2-furanyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-(3-furanyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-{5-(3-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-{5-(2-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-4-{4-(2-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2-Benzo[b]thienyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-(2-Benzo[b]furanyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2H)-furanone;

2-Ethyl-4-{5-(fluorothienyl)}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

4-{2-(5-Acetylthienyl)}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(5-methylthienyl)}-3(2H)-furanone;

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(3-methylthienyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-furanyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-furanyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(3-fluorofuranyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(2-fluorofuranyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(2-fluorofuranyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-thienyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-thienyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(2-fluorothienyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(2-fluorothienyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(3-fluorothienyl}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(2-benzo[b]thienyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-4-(2-benzo[b]furanyl)-2,2-dimethyl-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2dimethyl-4-(2-naphthyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(1-naphthyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-pyridyl)-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-methylpyrazolyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-ethylpyrazolyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-pyrazolyl)-3(2H)-furanone.

The above used terms and abbreviations are illustrated in the followingtable.

Term/Abbreviation Illustration Alkyl Linear or branched alkyl radicalhaving 1˜10 carbon atom(s). Haloalkyl Alkyl radical substituted with oneor more halogen atoms. Examples are fluoromethyl (F—CH₂—), 1-chloroethyl(CH₃—CHCl—), trifluoromethyl (CF₃—), and the like. Hydroxyalkyl Alkylradical substituted with one or more hydroxyl radicals. Examples arehydroxymethyl (HO—CH₂—), 2-hydroxyethyl (HO—CH₂CH₂—), and the like.Hydrido Single hydrogen atom. Halo Halogen atom such as fluorine,chlorine, bromine or iodine. Alkyloxy Alkyloxy radical with an alkylradical having 1˜10 carbon atom(s). Examples are methoxy, ethoxy,propoxy, iso-propoxy, t-butoxy, and the like. Alkyloxy is the same as“alkoxy”. Lower Denoting an alkyl radical of 1˜5 carbon atom(s), whenused with alkyl, haloalkyl, hydroxyalkyl, N-alkylamino, N-acylamino andthe like. For example, “lower haloalkyl” denotes “alkyl radical having1˜5 carbon atom(s) substituted with one or more halogen atom(s).Alkylthio Alkyl radical substituted with a sulfur atom. Examples aremethylthio (CH₃—S—), ethylthio (CH₃CH₂—S—), and the like. Alkylsulfonyl“—SO₂—” substituted with an alkyl radical. Examples are methylsulfonyl(CH₃—SO₂—), ethylsulfonyl (CH₃CH₂—SO₂—), and the like. Aminosulfonyl“—SO₂—” substituted with an amino (—NH₂) radical (NH₂—SO₂—).(N-Alkylamino)- “—SO₂—” substituted with an N-alkylamino sulfonylradical. Examples are (N-methylamino)sulfonyl (CH₃—NH—SO₂—),(N-ethylamino)sulfonyl, (CH₃CH₂—NH—SO₂—), and the like. (N-Acylamino)-Aminosulfonyl radical substituted with an acyl sulfonyl group at thenitrogen atom. Examples are (N-acetylamino)sulfonyl [CH₃C(O)—NH—SO₂—],(N-propionylamino)sulfonyl [CH₃CH₂C(O)—NH—SO₂—], and the like.Haloalkoxy Alkoxy radical substituted with one or more halogen atom(s).Examples are fluoromethoxy (FCH₂O—), 2-Chloroethoxy (ClCH₂—CH₂—O—),trifluoromethoxy (CF₃O—), and the like. Alkoxyalkyl Alkyl radicalsubstituted with an alkoxy radical. Examples are methoxymethyl(CH₃—O—CH₂—), 1-methoxy-n-propyl- [CH₃—CH₂—CH(OCH₃)—], and the like.Formyl “CHO—” radical. Acyl “—C(O)—” substituted with an alkyl radical.Examples are acetyl [CH₃—C(O)—], propionyl [CH₃CH₂—C(O)—], and the like.N-Acylamino “—NH—” substituted with an acyl radical. Examples areN-acetylamino [CH₃C(O)—NH—], N-propionylamino [CH₃CH₂C(O)—NH—], and thelike. Alkylsulfinyl “—S(O)—” substituted with an alkyl radical. Examplesare methylsulfinyl [CH₃—S(O)—], ethylsulfinyl [CH₃CH₂S(O)—], and thelike. Methylenedioxy “—O—CH₂—O—” radical. N,N-dialkylamino Amino radicalsubstituted with two alkyl radicals. Examples are N,N-dimethylamino[(CH₃)₂N—], N,N-methyl-ethylamino [CH₃—N—CH₂CH₃—], and the like.

General Synthetic Procedures

Most of the compounds of the present invention can be synthesizedaccording to the following procedures of Schemes I˜VIII, whereinsubstituents R₁˜R₁₉, X, Y, Z, and AR are as defined for Formula I,unless noted otherwise. Several compounds of this invention can beprepared by following procedures of Schemes I˜VIII with minormodifications, such as used reagents, solvents, and change in thesequence of reactions. Some compounds in this invention were synthesizedby following procedures which do not fall into the categories of SchemesI˜VIII, and the synthetic details for those compounds are described intheir individual preparation examples.

Scheme I shows the six step procedures used to prepare2,2-dialkyl-4-aryl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (g) fromcommercially or easily available starting material1,1-dialkyl-2-propyn-1-ol (a). In step one, the lithium acetylenide ofa, which is generated in situ at −78° C. by adding n-BuLi to the THFsolution of the starting material a, is reacted with4-(methylthio)benzaldehyde to afford the diol b. In step two, thebenzylic hydroxyl group of b is oxidized to the corresponding carbonylof c by using an oxidizing agent such as pyridinium dichromate,manganese dioxide, chromium trioxide, and the like. In step three, theacyclic ketone c is cyclized to give 3(2H)-furanone d by usingdiethylamine as a catalyst in alcoholic solvent [J. Chem. Soc. 3871(1958)]. In step four, the sulfide d is oxidized to the correspondingsulfone e by reacting with OXONE. In step five, halogenation of5-aryl-2,2-dialkyl-3(2H)-furanone e is carried out to afford f byreacting e either with bromine in acetic acid or with iodine, in thepresence of a catalytic amount of BTI[{bis(trifluoroacetoxy)iodo}benzene]. In step six, halide f is subjectedto palladium(0)-mediated aromatic coupling to afford diaryl compound g,by using a proper aryl boronic acid [Suzuki Coupling: J. Org. Chem. 59,5524 (1994)]. The order of the reactions in individual steps in all thereaction schemes may be changed as long as the overall process can givethe desired compound. For example, in Scheme I, the halogenation stepfive may be carried out first and then the oxidation step four isperformed instead of carrying out oxidation step four and then thehalogenation step five.

Scheme II shows the four step procedures to prepare4-aryl)-5-{4-(aminosulfonyl)phenyl}-3(2H)-furanone (k) from the sulfideintermediate d synthesized in Scheme I. In step one, partial oxidationof the sulfide d to the sulfoxide h is achieved by usingm-chloroperbenzoic acid (m-CPBA). In step two, the sulfoxide h issubjected to halogenation reaction by using either bromine in aceticacid or iodine in the presence of a catalytic amount of BTI as in SchemeI to give halide i. In step three, the halide i is then transformed intosulfonamide j by sequential treatments of i with 1) trifluoroaceticanhydride (TFAA), 2) triethylamine (TEA) in methanol, 3) chlorine inacetic acid, and then 4) ammonia water, according to the literature [J.Am. Chem. Soc. 73, 3240 (1951)]. In step four, the sulfonamide j iscoupled with a proper aromatic boronic acid in the presence of apalladium(0) catalyst (Suzuki coupling) to afford4,5-diaryl-3(2H)-furanone k.

Scheme III illustrates the three step procedures to synthesize4,5-diaryl-3(2H)-furanone (o), wherein 5-{4-(methylsulfonyl)phenyl}group is substituted with “X”. In step one, substituted thioanisole I isreacted with aromatic acetylchloride to afford the ketone m in thepresence of aluminum chloride (Friedel-Craft acylation). In step two,the ketone m is subjected to “C-acylation” with α-bromoisobutyrylcyanide using sodium hydride as a base. The acylation further proceedsto give the intramolecular cyclization product n. In step three, thesulfide n is oxidized by using OXONE to yield the methylsulfone o.Thioanisole I can be replaced with an (alkylthio)benzene derivative toexpand the scope of Scheme III to synthesize an alkylsulfone compoundanalogous to compound o. Furthermore the reaction sequence of Scheme IIIcan be changed, where the oxidation of the methylthio group (step 3) isperformed ahead of the reaction with α-bromoisobutyryl cyanide (step 2)to give the same target product o. Thus, several variations are possiblewith Scheme III to prepare compounds of this invention.

Scheme IV shows the two step procedures to synthesize sulfonamide q. Instep one, the methylsulfide n is reacted with m-CPBA to obtain thesulfoxide p. In step two, the sulfoxide p is converted into thesulfonamide q by reacting p sequentially with 1) trifluoroaceticanhydride, 2) triethylamine in methanol, 3) chlorine in acetic acid, andthen 4) ammonia water.

Scheme V illustrates the one step procedure to prepare the thiocarbonylcompound s. In Scheme V, the 4,5-diaryl-3(2H)-furanone r is reacted withLawesson's reagent to give the corresponding thiocarbonyl compound s.

Scheme VI shows the two step procedures to synthesize N-alkylsulfonamideu from the sulfoxide p. In step one, the sulfoxide p is converted intothe corresponding sulfonylchloride by reacting sequentially with 1)trifluoroacetic anhydride, 2) triethylamine in methanol, and then 3)chlorine in acetic acid. In step two, the reaction of the sulfonylchloride t with alkylamine yields the N-alkylsulfonamide u.

Scheme VII illustrates the one step procedure to synthesize theN-acylsulfonamide v. The sulfonamide q is reacted with an alkanoicanhydride in tetrahydrofuran to give v.

The reaction sequence of Scheme I can be modified to prepare5-{4-(methylthio)phenyl}-3(2H)-furanone x and5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone y, as described in thefollowing Scheme VIII.

The following examples contain detailed descriptions of the preparationmethods for compounds of Formula I-V. The detailed descriptions of theseexamples are presented illustrative purposes only and should not beinterpreted as a restriction to the present invention. Most of thesedetailed descriptions fall within the scope, and serve to exemplify, theabove described GENERAL SYNTHETIC PROCEDURES which form a part of theinvention. All the chromatographic separations in the presented exampleswere performed using silica gel unless noted otherwise. Theabbreviations used in the following examples are defined as in thefollowing table.

Abbreviation Denotation ° C. Degree in Celcious. mp Melting point.Uncorrected value. NMR Proton nuclear magnetic resonance. All the NMRspectra were taken with a 300 MHz NMR. The NMR solvent in this inventionis CDCl₃, unless noted otherwise. In presenting the NMR data of thisinvention, widely- accepted abbreviations were used as follows: s forsinglet, d for doublet, t for triplet, q for quartet, br s for broadsinglet, and so on. IR Infrared spectroscopy. All the IR spectra weretaken for the neat form on a KBr window and the unit is in cm⁻¹ unlessnoted otherwise. MS Mass spectroscopy. All the MS data are presented inthe m/e unit. FAB Fast atom bombardment. EI Electron ionization. THFTetrahydrofuran m Ion peak for molecular weight in the MS data. Thus(m + 1) corresponds to the peak of parent molecule with one proton.

EXAMPLE 1

2,2-Dimethyl-4-(4methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneStep 1: Preparation of1-{4-(methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-ol

To a stirred solution of 2-methyl-3-butyn-2-ol (416 mg) and dry THF (30ml) under argon and at −78° C., was added 1.6 M butyllithium in hexane(5 ml) dropwise over 10 minutes. 20 minutes later,p-methylthiobenzaldehyde (0.5 ml) was added dropwise to the reactionsolution. Then the reaction solution was allowed to warm up to theambient temperature by removing the cold bath. After stirring thereaction mixture for 2 hours, the reaction solvent was removed in vacuo,which was followed by neutralization with dilute aqueous HCl solution.The reaction mixture was then extracted with dichloromethane (50 ml×3),and the dichloromethane layer was washed with water (50 ml×1). Thedichlomethane layer was concentrated in vacuo and the resulting residuewas subjected to column chromatographic separation (hexane/ethylacetate=1:1) to yield 724 mg of1-{4-(methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-ol. NMR: δ1.54(s, 6H), 2.36 (s, 1H), 2.48 (s, 3H), 2.62 (d, 1H), 5.43(d, J=5.4 Hz,1H), 7.25 (d, J=6.9 Hz, 2H), 7.43 (d, J=6.9 Hz, 2H).

Step 2: Preparation of1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one

To 724 mg of 1-{4-(methylthio)phenyl}-4-hydroxy-4methyl-2-pentyn-1-oldissolved in 30 ml acetone, was slowly added dropwise 451 mg of chromiumtrioxide dissolved in 10 ml water and 0.25 ml concentrated sulfuricacid. After stirring the reaction solution overnight at the ambienttemperature, the reaction solution was concentrated in vacuo. Theresulting aqueous residue was extracted with 50 ml water anddichloromethane (50 ml×3). The organic layer was concentrated in vacuoand the resulting residue was subjected to column chromatographicseparation hexane/ethyl acetate=1:1) to yield 200 mg of1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one as a solid.mp: 102-103° C. NMR: δ1.67(s, 6H), 2.41 (s, 1H), 2.54 (s, 3H), 7.28 (d,J=8.7 Hz, 2H), 8.02 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3404, 1613, 1176, 747.

Alternatively,1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one was preparedby using PDC (pyridinium dichromate) in place of chromium trioxide asfollows: To a stirred suspension of1-{4-(methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-ol (20 g) andcelite (30 g) in 500 ml dichloromethane, was added PDC (40 g)portion-wise over 10 minutes. The reaction mixture was stirred for 12hours at room temperature. The suspension was then filtered throughFlorisil pad (150 g) and the Florisil pad was washed with 500 mlmethylene chloride. The filtrate was washed with dilute aqueous HCl (200ml×1) and the organic layer was concentrated in vacuo. The resultingresidue was chromatographed as above to afford 12.3 g of1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one.

Another variation of oxidation reaction to prepare1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one from1-{4-(methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-ol was performedas follows: A suspension of1-{4-(methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-ol (150 g) andactivated manganese dioxide (200 g) in methylene chloride (2 L) wasstirred using an overhead stirrer for 20 hours at room temperature. Thenthe suspension was filtered through celite (300 g) and the filtrate wasconcentrated under reduced pressure. The resulting crude solid wasrecrystallized from ethylacetate/hexane to afford 120 g of1-{(4methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one.

Step 3: Preparation of2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone

To a stirred solution of1-{(4-methylthio)phenyl}-4-hydroxy-4-methyl-2-pentyn-1-one (120 mg) in20 ml ethanol, was added dropwise diethylamine (0.08 ml) diluted in 7 mlethanol over 5 minutes at room temperature. The reaction solution wasstirred for another one hour and then the solvent was removed in vacuo.The resulting residue was diluted with 50 ml water and then extractedwith dicloromethane (30 ml×3). The organic layer was concentrated invacuo and the resulting residue was subjected to column chromatographicseparation (hexane/ethylacetate=4:1) to give 90 mg of2.2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone as a solid. mp:107-109° C. NMR: δ1.48 (s, 6H), 2.54 (s, 3H), 5.91 (s, 1H), 7.30 (d,J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H). IR (cm⁻¹): 1676, 1579, 1485,1376, 1174, 1095, 1050, 809.

Step 4: Preparation of4-bromo-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone

To a stirred solution of2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone (45 mg) in 20 mlcarbon tetrachloride, were added acetic acid (0.5 ml) and bromine (0.1ml). The reaction solution was stirred at room temperature for one hour.Then the reaction was quenched by adding 20 ml of saturated aqueoussodium thiosulfate solution to the reaction solution. After removing thecarbon tetrachloride in vacuo, the resulting aqueous layer was extractedwith dichloromethane (50 ml×3) and the organic layer was then washedwith water (50 ml×1). The organic layer was concentrated in vacuo andthe resulting residue was chromatographed (hexane/ethylacetate=2:1) toyield 69 mg of4-bromo-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone as a solid.NMR: δ1.52 (s, 6H), 2.55 (s, 3H), 7.33 (d, J=9.3 Hz, 2H), 8.15 (d, J=9.0Hz, 2H); IR (cm⁻¹): 1704, 1594, 1574, 1486, 1348, 1184, 1069.

Step 5: Preparation of4-bromo-2,2-dimethyl-5-{4-(4-methylsulfonyl)phenyl}-3(2H)-furanone

42 mg of 4-bromo-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanonewas dissolved in 15 ml THF and 15 ml ethanol, to which was added 178 mgof OXONE. The mixture was stirred overnight at room temperature. Thenthe solvent was removed in vacuo. The resulting residue was extractedwith 50 ml water and methylene chloride (50 ml×3). The organic layer wasconcentrated under reduced pressure and the resulting residue wassubjected to column chromatographic separation (hexane/ethylacetate=2:1)to afford 45 mg of desired4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone as asolid. mp: 196-196.5° C. NMR: δ1.57 (s, 6H), 3.11 (s, 3H), 8.11 (d,J=8.7 Hz, 2H), 8.40 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2928, 1703, 1559,1270, 1148, 1076, 847. MS (EI): 346 (m).

Step 6: Preparation of2,2-dimethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (110mg) and tetrakis(triphenylpalladium(0) (54 mg) in 30 ml benzene, wereadded 2 M aqueous sodium carbonate (0.22 ml) and 4-methyl-benzeneboronicacid (60 mg). The reaction solution was stirred at reflux for 24 hours.Then the solvent was evaporated off under reduced pressure. Theresulting residue was extracted with 50 ml water and dichloromethane (50ml×3). The organic layer was concentrated in vacuo and the resultingresidue was separated by column chromatography (hexane/ethylacetate=2:1)to give 76 mg of2,2-dimethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 167-168° C. NMR: δ1.57 (s, 6H), 2.38 (s, 3H), 3.07 (s,3H), 7.17 (m, 4H), 7.89 (m, 4H). IR (cm⁻¹): 1707, 1660, 1531, 1289,1230. MS (EI): 356 (m).

EXAMPLE 2

4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (112mg) and tetrakis(triphenylphosphine)palladium(0) (54 mg) in 7 ml benzeneand 1 ml ethanol, were added 2 M aqueous sodium carbonate (0.22 ml) and(3-chloro-4-fluorophenyl)boronic acid (82 mg). The reaction solution waskept at reflux for 24 hours. Then the solvent was evaporated off underreduced pressure. The resulting residue was extracted with 50 ml waterand dichloromethane (50 ml×3). The organic layer was concentrated invacuo and the resulting residue was separated by column chromatography(hexane/ethylacetate) to yield 32 mg of4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 162-164° C. NMR: δ1.58 (s, 6H), 3.09 (s, 3H), 7.13 (m,2H), 7.40 (d, J=6.6 Hz, 1H), 7.83 (d, J=8.1 Hz, 2H), 7.97 (d, J=8.1 Hz,2H). IR (cm⁻¹): 2930, 1700, 1587, 1503, 1404, 1317, 1150, 1068, 913,771, 744.

EXAMPLE 3

2,2-Dimethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (220mg), 1,3-bis(diphenylphosphino)propane (24 mg) and palladium(II) acetate(6.1 mg) in 30 ml benzene, were added 2 M aqueous sodium carbonate (0.22ml) and 4-methoxybenzeneboronic acid (90 mg). The reaction solution waskept at reflux for 24 hours. Then the solvent was removed under reducedpressure. The resulting residue was purified by a procedure similar tothe purification method in Example 2 to yield 55 mg of2,2-dimethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. NMR: δ1.56 (s, 6H), 3.07 (s, 3H), 3.83 (s, 3H), 6.92 (d,J=8.7 Hz, 2H), 7.23 (d, J=9.0 Hz, 2H), 7.89(dd, J=8.7, 8.7 Hz, 4H). IR(cm⁻¹): 2925, 1697, 1592, 1149, 1031, 912, 745.

EXAMPLE 4

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (170mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of saturated aqueoussodium bicarbonate, and 100 mg of 3-fluorobenzeneboronic acid. Thereaction solution was stirred at 90° C. for 12 hours. Then the solventwas removed under reduced pressure. The resulting residue was extractedwith water and dichloromethane. The organic layer was concentrated invacuo and the resulting residue was separated by column chromatography(hexane/ethylacetate) to yield 120 mg of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 178-179° C. NMR: δ1.58 (s, 6H), 3.08 (s, 3H), 7.05 (m,3H), 7.33 (m, 1H), 7.83 (d, J=8.7 Hz, 2H), 7.95 (d, J=8.4 Hz, 2H). IR(cm⁻¹): 3020, 1697, 1620, 1403, 1318, 1149, 958, 768. MS (FAB): 361(m+1).

Alternatively, the titled compound was prepared as described in thefollowing procedure: 3.0 g of2,2-dimethyl-4(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone(Example 166) was dissolved in 50 ml THF, 50 ml methanol and 50 ml wateralong with 10 g of OXONE. The reaction mixture was stirred at roomtemperature for 2 hours. Then the solution was concentrated in vacuo andthe resulting aqueous solution was extracted with 150 ml methylenechloride. The organic layer was washed with brine and then was driedover anhydrous magnesium sulfate. The magnesium sulfate was removed byfiltration and the filtrate was concentrated in vacuo. The resultingresidue was recrystallized from methylene chloride/hexane to afford 3.3g of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.

Another variation to prepare2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanonewas performed starting from2-(3-fluorophenyl)-1-{4-(methylsulfonyl)phenyl}-ethanone as follows: Toa stirred solution of2-(3-fluorophenyl)-1-(4-methylsulfonylphenyl)-ethanone (1 g) in 10 ml ofTHF, was added 0.23 g of 95% sodium hydride at 0° C. The reactionsolution was stirred for 1 hour at the same temperature. Then 0.64 g ofa-bromo-isobutyric cyanide was added dropwise to the reaction mixture at0° C. The reaction mixture was stirred for another 7 hours while beingallowed to warm to room temperature. Then the reaction was quenched with5 ml of water. The mixture was concentrated in vacuo, and was dissolvedin 50 ml of water. The aqueous solution was extracted with ethylacetate(100 ml). The organic layer was washed with brine, concentrated invacuo. Then the resulting residue was purified by column chromatography(hexane/ethylacetate) to afford 0.75 g of2,2-dimethyl-4-(3-fluorophenyl)-5-{(methylsulfonyl)phenyl}-3(2H)-furanone.

EXAMPLE 5

4-(3-acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (170mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of saturated aqueoussodium carbonate, and 130 mg of 3-acetylbenzeneboronic acid. Thereaction solution was stirred at 90° C. for 12 hours. Then the solventwas removed under reduced pressure. The resulting residue was extractedwith water and dichloromethane. The organic layer was concentrated invacuo and the resulting residue was separated by column chromatography(hexane/ethylacetate=2:1) to afford 100 mg of4-(3-acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 189-190° C. NMR: δ1.60 (s, 6H), 2.59 (s, 3H), 3.07 (s,3H), 7.48 (m, 2H), 7.82 (d, J=8.7 Hz, 2H), 7.90 (m, 2H), 7.94 (d, J=8.4Hz, 2H). IR (cm⁻¹): 1690, 1620, 1589, 1149, 958, 770.

EXAMPLE 6

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-nitrophenyl)-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (170mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of saturated aqueoussodium carbonate, and 120 mg of 3-nitrobenzeneboronic acid. The reactionsolution was stirred at 90° C. for 12 hours. Then the solvent wasremoved under reduced pressure. The resulting residue was extracted withwater and dichloromethane (50 ml×3). The organic layer was concentratedin vacuo and the resulting residue was separated by columnchromatography (hexane/ethylacetate) to afford 100 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-nitrophenyl)-3(2H)-furanoneas a solid. mp: 158-159° C. NMR: δ1.61 (s, 6H), 3.09 (s, 3H), 7.57 (t,J=7.8 Hz, 1H), 7.64 (m, 1 H), 7.81 (d, J=9.0 Hz, 2H), 7.98 (d, J=8.7 Hz,2H), 8.19 (m, 2H). IR (cm⁻¹): 2982, 1697, 1529, 1403, 1349, 1150, 959,770.

EXAMPLE 7

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethoxy)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (150mg) in 15 ml toluene and 5 ml ethanol, were added 30 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of saturated aqueoussodium carbonate, and 100 mg of 4-(trifluoromethoxy)benzeneboronic acid.The reaction solution was stirred at 90° C. for 24 hours. Then thesolvent was removed under reduced pressure. The resulting residue wasextracted with water and dichloromethane. The organic layer wasconcentrated in vacuo and the resulting residue was separated by columnchromatography (hexane/ethylacetate) to yield 60 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethoxy)phenyl}-3(2H)-furanoneas a solid. mp: 118-120° C. NMR: δ1.58 (s, 6H), 3.08 (s, 3H), 7.20-7.26(m, 2H), 7.31-7.34 (m, 2H), 7.82-7.85 (m, 2H), 7.95-7.98 (m, 2H). IR(cm⁻¹): 2931, 1698, 1510, 1387, 1258, 1150, 960, 846, 770.

EXAMPLE 8

2,2-Dimethyl-4-(3,4-methylenedioxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of saturated aqueoussodium carbonate, and 150 mg of (3,4-methylenedioxy)benzeneboronic acid.The reaction solution was stirred at 90° C. for 12 hours. Then thesolvent was removed under reduced pressure. The resulting residue wasextracted with water and dichloromethane. The organic layer wasconcentrated in vacuo and the resulting residue was separated by columnchromatography (hexane/ethylacetate) to yield 100 mg of2,2-dimethyl-4-(3,4-methylenedioxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 178-179° C. NMR: δ1.60 (s, 6H), 3.07 (s, 3H), 5.99 (s,2H), 6.74 (m, 2H), 6.84 (d, J=8.7 Hz, 1H), 7.87 (d, J=8.7 Hz, 2H), 7.94(d, J=8.7 Hz, 2H). IR (cm⁻¹): 1697, 1503, 1404, 1245, 1148, 959, 770.

EXAMPLE 9

2,2-Dimethyl-4-{4-(3-fluorophenyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 170 mg of {(3-fluoro-4-phenyl)benzene}boronic acid by aprocedure similar to the synthetic procedure in Example 2 to yield 110mg of2,2-dimethyl-4-{(3-fluoro-4-phenyl)phenyl}-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanoneas a solid. mp: 163-164° C. NMR: δ1.60 (s, 6H), 3.09 (s, 3H), 7.13 (m,2H), 7.41 (m, 2H), 7.45 (m, 2H), 7.57 (m, 2H), 7.91 (d, J=8.7 Hz, 2H),7.98 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3020, 1698, 1621, 1402, 1319, 1258,1148, 957, 770.

EXAMPLE 10

4-(4-Acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200mg) was coupled with 104 mg of (4-acetylbenzene)boronic acid accordingto a procedure similar to the synthetic procedure in Example 2 to yield55 mg of4-(4acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 164-167° C. NMR: δ1.60 (s, 6H), 2.32 (s, 3H), 3.08 (s,3H), 7.39-7.4 (m, 2H), 7.81-7.84 (m, 2H), 7.94-7.98 (m, 4H). IR (cm⁻¹):1696, 1685, 1618, 1386, 1318, 1150, 960, 770.

EXAMPLE 11

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (300mg) in 30 ml toluene and 10 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of aqueous 2M sodiumcarbonate, and 200 mg of (3,5-difluorobenzene)boronic acid. The reactionsolution was stirred at 90° C. for 12 hours. Then the solvent wasremoved under reduced pressure. The resulting residue was extracted withwater and dichloromethane. The organic layer was concentrated in vacuoand the resulting residue was separated by column chromatography(hexane/ethylacetate) to give 200 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 141-142° C. NMR: δ1.60 (s, 6H), 3.08 (s, 3H), 3.95 (s,3H), 6.92 (m, 3H), 7.88 (d, J=8.7 Hz, 2H), 7.93 (d, J=8.7 Hz, 2H). IR(cm⁻¹): 1695, 1611, 1516, 1316, 1270, 1123, 1023, 858, 769. MS (FAB):379 (m+1).

Alternatively, 18 g of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{4-(methylthio)-phenyl}-3(2H)-furanone(Example 173) was reacted with 45 g of OXONE in 300 ml THF, 300 mlethanol and 300 ml water according to a procedure similar to thealternative procedure of Example 4 to afford 19.5 g of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.

EXAMPLE 12

2,2-Dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

300 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 250 mg of (3,5-dimethyl-4-methoxybenzene)boronic acidaccording to a procedure similar to the procedure in Example 2 to give60 mg of2,2-dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 130-131° C. NMR: δ1.56 (s, 6H), 2.26 (s, 6H), 3.07 (s,3H), 3.75 (s, 3H), 6.91 (s, 2H), 7.87 (d, J=8.7 Hz, 2H), 7.92 (d, J=8.7Hz, 2H). IR (cm⁻¹): 2929, 1697, 1591, 1399, 1319, 1149, 1135, 771.

EXAMPLE 13

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(1-naphthyl)-3(2H)-furanone

200 mg of4bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 114 mg of naphthalene-1-boronic acid by a procedure similarto the procedure employed for Example 2 to afford2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(1-naphthyl)-3(2H)-furanoneas a solid. mp: 194-195° C. NMR: δ1.67 (s, 3H), 1.71 (s, 3H), 2.97 (s,3H), 7.33-7.43 (m, 2H), 7.48-7.60 (m, 2H), 7.51-7.52 (m, 1H), 7.66-7.69(m, 2H), 7.76-7.78 (m, 2H), 7.90-7.94 (m, 2H), IR (cm⁻¹): 1698, 1404,1318, 1149, 1092, 772.

EXAMPLE 14

2,2-Dimethyl-5-{4-methylsulfonyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 150 mg of (3-trifluoromethylbenzene)boronic acid by aprocedure similar to the synthetic procedure in Example 2 to afford 100mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanoneas a solid. mp: 115-116° C. NMR: δ1.60 (s, 6H), 3.08 (s, 3H), 7.49 (m,2H), 7.60 (m, 2H), 7.82 (d, J=8.7 Hz, 2H), 7.96 (d, J=9.0 Hz, 2H). IR(cm⁻¹): 1697, 1624, 1385, 1327, 124, 959, 770. MS (FAB): 411 (m+1).

Alternatively, 1.5 g of2,2-dimethyl-5-{4-(methylthio)phenyl}-4-{3-trifluoromethyl)phenyl}-3(2H)-furanone(Example 169) was reacted with 4.5 g of OXONE in 50 ml THF, 50 mlethanol and 50 ml water by following a procedure employed for thealternative synthesis of Example 4 to afford 1.28 g of the titledcompound.

EXAMPLE 15

4-(2-Benzo[b]thienyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 125 mg of (2-benzo[b]thienyl)boronic acid according to aprocedure similar to the procedure in Example 2 to afford 60 mg of4-(2-benzo[b]thienyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 204-206° C. NMR: δ1.61 (s, 6H), 3.11 (s, 3H), 7.32˜7.43(m, 4H), 7.51˜7.53 (m, 1H), 7.74˜7.84 (m, 2H), 8.01 (s, 2H). IR (cm⁻¹):1702, 1620, 1382, 1147, 957, 750.

EXAMPLE 16

4-(2-Benzo[b]furanyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 107 mg of (2-benzo[b]furan)boronic acid by following aprocedure similar to the synthetic procedure in Example 2 to afford 15mg of4-(2-benzo[b]furanyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 140-141° C. NMR: δ1.60 (s, 6H), 3.13 (s, 3H), 7.22-7.35(m, 4H), 7.60-7.63 (m, 1H), 8.06 (m, 4H). IR (cm⁻¹): 1703, 1538, 1406,1317, 1149, 958, 752.

EXAMPLE 17

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}4-(3-thienyl)-3(2H)-furanone

200 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 100 mg of thiophene-3-boronic acid according to a proceduresimilar to the synthetic procedure in Example 2 to yield 10 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanoneas a solid. NMR: δ1.56 (s, 6H), 3.09 (s, 3H), 6.92-6.93 (m, 1H),7.32-7.35 (m, 1H), 7.51-7.52 (m, 1H), 7.90-7.93 (m, 2H), 7.97-8.00 (m,2H).

EXAMPLE 18

2,2-Dimethyl-4-(2-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneStep 1: Preparation of2,2-dimethyl-4-iodo-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

25 g of 2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone, whichwas prepared by the OXONE oxidation of2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone by a proceduresimilar to Step 5 of Example 1, was dissolved in 400 ml carbontetrachloride and 100 ml chloroform, to which were added 25 g of[bis(trifluoroacetoxyl)iodo]benzene [BTI] and 15 g of iodine. Themixture was stirred for 3 hours at room temperature and then thereaction was quenched by adding saturated aqueous sodium thiosulfateuntil the characteristic color of iodine disappeared. The solution wasextracted with chloroform (500 ml×3) and the organic layer wasconcentrated in vacuo. The resulting residue was recrystallized fromhexane and ethylacetate to yield 35 g of2,2-dimethyl-4-iodo-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone. mp:184-185° C. NMR: δ1.55 (s, 6H), 3.12 (s, 3H), 8.12 (d, J=8.7 Hz, 2H),8.40 (d, J=8.7 Hz, 2H).

Step 2: Preparation of2,2-dimethyl-4-(2-furanyl)-5-{4-(metylsulfonyl)phenyl}-3(2H)-furanone

250 mg of2,2-dimethyl-4-iodo-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone was 86mg of furan-2-boronic acid by a procedure similar to the procedure inExample 2 to afford 47 mg of2,2-dimethyl-4-(2-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. NMR: δ1.56 (s, 6H), 3.11 (s, 3H), 6.51 (m, 1H), 6.89 (d,J=3.6 Hz, 1H), 7.37 (d, J=3.6 Hz, 1H), 7.97 (m, 4H). IR (cm⁻¹): 2989,1703, 1409, 1317, 2989, 1703, 1409, 1317, 1148, 959, 771.

EXAMPLE 19

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone

To a stirred solution of4-bromo-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200mg) in 15 ml toluene and 5 ml ethanol, were added 27 mg oftris(dibenzylidenacetone)dipalladium(0)-chloroform adduct, 17 mg oftriphenyl phosphine, 5 ml of aqueous 2M sodium carbonate, and lithium3-trimethylpyridinium boronate (200 mg). The reaction solution wasstirred at 90-100° C. for 24 hours. Then the solvent was removed invacuo. The resulting residue was extracted with water anddichloromethane (100 ml×3). The organic layer was concentrated in vacuoand the resulting residue was separated by column chromatography(hexane/ethylacetate) to afford 110 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanoneas a solid. mp: 164-166° C. NMR: δ1.60 (s, 6H), 3.09 (s, 3H), 7.38-7.42(m, 1H), 7.76-7.79 (m, 1H), 7.80-7.83 (m, 2H), 7.96-7.99 (m, 2H),8.42-8.49 (m, 1H), 8.56-8.61 (m, 1H). IR (cm⁻¹): 1698, 1386, 1316, 1149,1061, 961, 772.

EXAMPLE 20

2,2-Dimethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl)-3(2H)-furanone

To a stirred solution of2,2-dimethyl-4-iodo-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (445 mg)in 50 ml toluene and 15 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 15 ml of aqueous 2M sodiumcarbonate, and 547 mg of {4-(1-N-methylpyrazolyl)}-trimethylboronatelithium salt. The reaction solution was stirred at 90° C. for 12 hours.Then the solvent was removed in vacuo. The resulting residue wasextracted with water and dichloromethane (50 ml×3). The organic layerwas concentrated in vacuo and the resulting residue was separated bycolumn chromatography (hexane/ethylacetate) to give 290 mg of2,2-dimethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 114-115° C. NMR: δ1.54 (s, 6H), 3.10 (s, 3H), 3.94 (s,3H), 7.34 (s, 1H), 7.99-8.06 (m, 4H). IR (cm⁻¹): 2930, 1700, 1538, 1314,1148, 884, 771. MS(FAB): 347(m+1)

EXAMPLE 21

2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazolyl)-3(2H)-furanoneStep 1: Preparation of 4-bromo-1-N-tritylpyrazole

A mixture of 0.5 g of 4-bromopyrazole and 1.43 g of tritylchloride in 30ml of pyridine was stirred at reflux for 18 hours. The pyridine wasremoved in vacuo and the resulting residue was purified by silica columnchromatography (ethylacetate/hexane=1:1) to yield 1.32 g of4-bromo-1-N-tritylpyrazole.

Step 2: Preparation of {4-(1-N-tritylpyrazolyl)}-trimethylboronatelithium salt

To a stirred solution of the 4-bromo-1-N-tritylpyrazole in 30 ml dry THFat −78° C., was added dropwise 1.4 ml of 2 M butyllithium in hexane.Then the reaction mixture was stirred for 30 minutes, followed by theaddition of 0.76 ml of triisopropylborate. The reaction mixture wasstirred for another hour. Then the reaction was stopped by adding 20 mlmethanol. The solvent was removed in vacuo, and the resulting salt wasused in the next step without further purification.

Step 3: Preparation of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(1-N-tritylpyrazol)}-3(2H)-furanone

To 300 mg of2,2-dimethyl-4-iodo-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone in 50 mltoluene and 15 ml ethanol, were added 25 mg oftetrakis(triphenylphosphine)palladium(0), 15 ml 2M aqueous sodiumcarbonate, and 480 mg of the crude{4-(1-N-tritylpyrazolyl)}-trimethylboronate lithium salt from theprevious step. The reaction mixture was stirred at 90° C. for 12 hours.The reaction mixture was purified by a procedure similar to thepurification procedure in Example 2 to yield 120 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(1-N-tritylpyrazole)}-3(2H)-furanone.

Step 4: Preparation of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazoyl)-3(2H)-furanone

120 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(1-N-tritylpyrazolyl)}-3(2H)-furanonewas stirred in 23 ml methanol for 3 hours in the presence of 36 mg ofp-toluenesulfonic acid. Then the methanol was removed under reducedpressure and the resulting residue was diluted with 30 ml water. Theaqueous layer was extracted with dichloromethane (30 ml×3). The organiclayer was then concentrated in vacuo and the resulting residue waspurified by column chromatography (hexane/ethylacetate=1:4) to afford 60mg of2,2-dimethyl-5-{4-(methylsulfonyl)-phenyl}-4-(4-pyrazolyl)-3(2H)-furanone.NMR: δ1.56 (s, 6H), 3.11 (s, 3H), 7.88 (s, 2H), 8.05 (m, 5H). IR (cm⁻¹):3325, 1702, 1408, 1316, 1148, 913.

EXAMPLE 22

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanoneStep 1: Preparation of2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a stirred solution of2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone (10 g) in 200 mldichloromethane at 0° C., was added slowly dropwise 4.8 g ofm-chloroperoxybenzoic acid (m-CPBA) dissolved in 50 ml dichloromethane.After the reaction mixture was stirred at 0° C. for another two hours,the reaction solution was concentrated in vacuo. The resulting residuewas extracted with water and dichloromethane (50 ml×3), followed bywashing with aqueous sodium carbonate. The organic layer wasconcentrated and the crude product was purified by column chromatography(hexane/ethylacetate) to obtain 7.5 g of2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone as a solid. mp:108-109° C. NMR: δ1.51 (s, 6H), 2.78 (s, 3H), 6.06 (s, 1H), 7.78 (d,J=8.4 Hz, 2H), 8.02 (d, J=8.4 Hz, 2H). IR (cmu⁻¹): 2925, 1697, 1603,1558, 1173, 1087, 1049.

Step 2: Preparation of2,2-dimethyl-4-iodo-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a stirred solution of 6 g of2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone in 200 mlcarbon tetrachloride and 100 ml chloroform, were added 5.15 g of[bis(trifluoroacetoxy)iodo]benzene (BTI) and 6.5 g of iodine. Thereaction solution was stirred at room temperature. After 4 hours, thereaction was quenched by adding saturated aqueous sodium thiosulfateuntil the characteristic color of iodine disappeared. The quenchedsolution was extracted with water and dichloromethane (100 ml×3). Theorganic layer was concentrated in vacuo and the resulting crude productwas recrystallized from hexane/ethylacetate to yield 4.5 g of2,2-dimethyl-4-iodo-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone. NMR:δ1.53 (s, 6H), 2.79 (s, 3H), 7.81 (d, J=8.1 Hz, 2H), 8.38 (d, J=8.1 Hz,2H). IR (cm⁻¹): 2975, 2929, 1699, 1595, 1404, 1319, 1150, 969, 766, 552.

Step 3: Preparation of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanone

1.11 g of2,2-dimethyl-4-iodo-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone wasreacted with 30 ml trifluoroacetic anhydride (TFAA) for 2 hours at 0° C.After the volatile solvent was removed in vacuo, the resulting residuewas dissolved in 50 ml of 1:1 methanol/triethylamine. The solvent wasremoved again in vacuo. Then the resulting residue was dissolved in 30ml carbon tetrachloride, to which was added slowly 40 ml acetic acidsaturated with chlorine at 0° C. After stirring the reaction solution at0° C. for 20 minutes, the reaction solvent and the unreacted chlorinewere removed in vacuo. The resulting residue was dissolved in 30 mltoluene and the toluene was removed again under reduced pressure. Theresulting residue was reacted with 3 ml ammonia water in 40 ml THF at 0°C. for 30 minutes. The reaction solution was concentrated in vacuo andthe resulting residue was diluted with 30 ml water. The aqueous solutionwas then extracted with dichloromethane (30 ml×3). The organic layer wasconcentrated under reduced pressure and was purified by columnchromatography (hexane/ethylacetate=3:2) to obtain 450 mg of5-{4-(aminosulfonyl)-phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanone as asolid. mp: 179-180° C. NMR: δ1.50 (s, 6H), 5.63 (br. s, 2H), 8.05 (dd,J=9.0, 1.5 Hz, 2H), 8.29 (dd, J=9.0, 5.7 Hz, 2H). IR (cm⁻¹): 3367, 3261,2985, 1684, 1582, 1405, 1188, 913. MS (FAB): 393 (m+1).

Step 4: Preparation of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone

To stirred solution of 100 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanone dissolvedin 15 ml toluene and 5 ml ethanol, were added 34 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2M aqueous sodiumcarbonate, and 80 mg of (4-fluorobenzene)boronic acid. The reactionsolution was then stirred at 95° C. for 24 hours, followed by removal ofthe solvent in vacuo. Then the residue was extracted with 30 ml waterand dichloromethane (30 ml×3). The organic layer was dried overanhydrous magnesium sulfate. Then the hydrated magnesium sulfate wasfiltered off and the filtrate was concentrated in vacuo. The resultingcrude product was purified by column chromatography(hexane/ethylacetate=1:1) to give 40 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanoneas a solid. mp: 162-163° C. NMR: δ1.57 (s, 6H), 4.93 (br. s, 2H), 7.08(d, J=8.7 Hz, 2H), 7.25 (t, J=8.7 Hz, 2H), 7.78 (d, J=8.7 Hz, 2H), 7.92(d, J=8.7 Hz, 2H). IR (cm⁻¹): 3348, 3263, 1685, 1589, 1341, 1219, 1163.

EXAMPLE 23

5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone

To a stirred solution of 100 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanone dissolvedin 15 ml toluene and 5 ml ethanol, were added 30 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate, and 100 mg of 3-(trifluoromethyl)benzeneboronic acid. Thenthe mixture was stirred at 95° C. for 24 hours. The reaction mixture waspurified according to a procedure similar to Step 4 of Example 22 toyield 35 mg of5-{4-(aminosulfonyl)phenyl}2,2-dimethyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone.mp: 129-130° C. NMR: δ1.59 (s, 6H), 4.93 (br, s, 2H), 7.48 (m, 2H), 7.59(m, 2H), 7.76 (d, J=8.7 Hz, 2H), 7.93 (d, J=9.0 Hz, 2H). IR (cm⁻¹):3343, 3265, 1691, 1593, 1329, 1262.

EXAMPLE 24

5-{4-(Aminosulfonyl)phenyl}-4-{3,4-(dimethoxy)phenyl}-2,2-dimethyl3(2H)-furanone

To a stirred solution of 150 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanone dissolvedin 15 ml toluene and 5 ml ethanol, were added 20 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate, and 100 mg of 3,4-(dimethoxy)benzeneboronic acid. And themixture was stirred at 95° C. for 24 hours. The reaction mixture waspurified by following a procedure similar to Step 4 of Example 22 togive 60 mg of5-{4-(aminosulfonyl)phenyl}-4-{3,4-(dimethoxy)phenyl}-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 213-214° C. NMR: δ1.57 (s, 6H), 3.81 (s, 3H), 3.90 (s,3H), 4.87 (br s, 2H), 6.86 (m, 3H), 7.81 (d, J=8.4 Hz, 2H), 7.91 (d,J=8.7 Hz, 2H). IR (cm⁻¹): 3339, 3248, 1694, 1404, 1259, 1159, 1024, 604.

EXAMPLE 25

4-(3-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone

150 mg of 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanonewas reacted with 75 mg of (3-acetylbenzene)boronic acid by following aprocedure similar to Step 4 of Example 22 to yield 40 mg of4-(3-acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 217-218° C. NMR: δ1.57 (s, 6H), 2.58 (s, 3H), 4.89 (brs, 2H), 7.48 (m, 2H), 7.78 (m, 2H), 7.91 (m, 4H). IR (cm⁻¹): 3340, 3233,1682, 1558, 1162, 801, 751, 679, 654, 604. MS (FAB): 393 (m+1).

EXAMPLE 26

4-{3-N-(Acetylamino)phenyl}-5-{4-(aminosulfonyl)phenyl)-2,2-dimethyl-3(2H)-furanone

60 mg of 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanonewas reacted with 35 mg of {3-N-(acetylamino)benzene}boronic acid byfollowing a procedure similar to Step 4 of Example 22 to give 25 mg of4-{3-N-(acetylamino)phenyl}-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 225-227° C. NMR: δ1.62 (s, 6H), 2.04 (s, 3H), 4.82 (brs, 2H), 7.4 (m, 3H), 7.53 (m, 1H), 7.68 (m, 4H). IR (cm⁻¹): 3325, 2926,1698, 1558, 1437, 1119.

EXAMPLE 27

5-{4-(Aminosulfonyl)phenyl{-2,2-dimethyl-4-}3,4-(methylenedioxy)phenyl}-3(2H)-furanone

120 mg of 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanonewas reacted with 100 mg of 3,4-(methylenedioxy)benzeneboronic acid byfollowing a procedure similar to Step 4 of Example 22 to yield 40 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-{3,4-(methylenedioxy)phenyl}-3(2H)-furanoneas a solid. mp: 178-179° C. NMR: δ1.56 (s, 6H), 4.89 (br s, 2H), 5.99(s, 2H), 6.74 (m, 2H), 6.83 (m, 1H), 7.82 (d, J=9.0 Hz, 2H), 7.92 (d,J=9.0 Hz, 2H). IR (cm⁻¹): 3237, 1682, 1338, 1245, 1164.

EXAMPLE 28

5-{4-(Aminosulfonyl)phenyl{-4(2-benzo[b]thienyl)-2,2-dimethyl-3(2H)-furanone

200 mg of 5-{4-(aminosulfonyl)phenyl}-2,2dimethyl-4-iodo-3(2H)-furanonewas coupled with 109 mg of (2-benzo[b]thiophene)boronic acid byfollowing a procedure similar to Step 4 of Example 22 to yield 45 mg of5-{4-(aminosulfonyl)phenyl}-4-(2-benzo[b]thienyl)-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 120-121° C. NMR: δ1.60 (s, 3H), 4.89 (br s, 2H), 7.36(m, 2H), 7.50 (m, 1H), 7.75 (m, 2H), 7.97 (m, 4H). IR (cm⁻¹): 3350,3210, 1650, 1530, 1320, 1158, 803, 743. MS (FAB): 400 (m+1).

EXAMPLE 29

5-{4-(Aminosulfonyl)phenyl}-4-(3-biphenyl)-2,2-dimethyl-3(2H)-furanone

200 mg of 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanonewas reacted with 120 mg of (3-phenylbenzene)boronic acid by following aprocedure similar to Step 4 of Example 22 to give 40 mg of5-{4-(aminosulfonyl)phenyl}-4-(3-biphenyl)-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 160-161° C. NMR: δ1.57 (s, 6H), 4.86 (br s, 2H), 7.23(m, 1H), 7.34 (m, 1H), 7.44 (m, 3H), 7.56 (m, 4H), 7.84 (d, J=8.7 Hz,2H), 7.91 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3249, 1681, 1614, 1345, 1161.

EXAMPLE 30

5-{4-(Aminosulfonyl)phenyl{-4-(2-benzo[b]furanyl)-2,2-dimethyl-3(2H)-furanone

200 mg of 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)-furanonewas coupled with 99 mg of benzo[b]furan-2-boronic acid by following aprocedure similar to Step 4 of Example 22 to give 45 mg of5-{4-(aminosulfonyl)phenyl}-4-(2-benzo[b]furanyl)-2,2-dimethyl-3(2H)-furanoneas a solid. mp: 143-145° C. NMR: δ1.60 (s, 6H), 4.92 (br s, 2H), 7.23(m, 3H), 7.72 (m, 2H), 8.02 (m, 4H), IR (cm⁻¹): 3384, 3245, 1698, 1510,1253, 1161, 793.

EXAMPLE 31

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanoneStep 1: Preparation of4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol

To a stirred solution of 3-methyl-1-pentyn-3-ol (23.3 g) in 150 mlanhydrous THF at −78° C. under argon, was added 130 ml of 2.5 Mbutyllithium in hexane dropwise over 20 minutes. The reaction solutionwas stirred for another 20 minutes, followed by dropwise addition 16 mlof 4-methylthiobenzaldehyde. After stirring for another 2 hours, thereaction was quenched by adding 200 ml of dilute aqueous HCl. Thereaction solvent was removed in vacuo, and the resulting aqueoussolution was extracted with dichloromethane (100 ml×3). The organiclayer was concentrated under reduced pressure and the resulting residuewas purified by column chromatography (hexane/ethylacetate=1:1) to yield30 g of 4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol as an oil.NMR: δ1.05 (t, J=7.5 Hz, 3H), 1.51 (s, 3H), 1.73 (m, 2H), 2.18 (s, 1H),2.50 (s, 3H), 5.49 (s, 1,H), 7.26 (d, J=8.7 Hz, 2H), 7.45 (d, J=8.7 Hz,2H). IR (cm⁻¹): 3348, 2974, 2930, 1492, 1092, 983, 795, 523.

Step 2: Preparation of4-hydroxy-4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1-one

To 9.9 g of 4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol dissolvedin 200 ml dichloromethane, were added 15 g of pyridinium dichromate(PDC) and 15 g of celite. The suspension was stirred overnight at roomtemperature, and then the insoluble material was filtered off throughFlorisil. The filtrate was purified by column chromatography(hexane/ethylactate=4:1) to give 5.34 g of4-hydroxy-4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1-one. NMR: δ1.13(t, J=7.5 Hz, 3H), 1.62 (s, 3H), 1.85 (q, J=7.8 Hz, 2H), 2.54 (s, 3H),7.28 (d, J=8.7 Hz, 2H), 8.01 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3427, 2974,1588, 1095, 914, 745.

Step 3: Preparation of2-ethyl-2-methyl-5-{4-(methylthio)phenyl}-3(2H)-furanone

5.34 g of 4-hydroxy-4-methyl-1-{4-(methylthio)phenyl}-2-hexyn-1-one wasdissolved in 200 ml ethanol, added dropwise 3 ml diethylamine dilutedwith 50 ml ethanol. The reaction solution was stirred at roomtemperature for 4 hours, and the solvent was removed in vacuo. Theresulting residue was extracted with water and dichloromethane (100ml×3). Concentration of the organic layer afforded crude2-ethyl-2-methyl-5-{4-(methylthio)phenyl}-3(2H)-furanone, which was usedin the next step without further purification.

Step 4: Preparation of2-ethyl-2-methyl-5-{4-(methylsufonyl)phenyl}-3(2H)furanone

The crude product2-ethyl-2-methyl-5-{4-(methylthio)phenyl}-3(2H)-furanone from theprevious Step 3 was dissolved in 50 ml ethanol, 50 ml THF and 50 mlwater, and 10 g of OXONE was added thereto. The reaction mixture wasstirred overnight at room temperature. Then the insoluble materials wereremoved by filtration and the filtrate was concentrated in vacuo. Theresulting aqueous layer was extracted with dichloromethane (100 ml×1 and50 ml×2). The organic layer was concentrated under reduced pressure andthe resulting residue was purified by column chromatography(hexane/ethylacetate=2:1) to yield 4.5 g of2-ethyl-2-methyl-5-{4-(methylsufonyl)phenyl}-3(2H)-furanone. NMR: δ0.89(t, J=7.2 Hz, 3H), 1.48 (s, 3H), 1.91 (q, J=7.2 Hz, 2H), 3.11 (s, 3H),6.13 (s, 1H), 8.07 (m, 4H).

Step 5: Preparation of4-bromo-2-ethyl-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To 4.5 g of 2-ethyl-2-methyl-5-{4-(methylsufonyl)phenyl}-3(2H)-furanonedissolved in 100 ml carbon tetrachloride, were added acetic acid (3 ml)and bromine (1 ml). The reaction solution was stirred for 1 hour at roomtemperature. Then the reaction was quenched by adding saturated aqueoussodium thiosulfate solution until the characteristic color of brominedisappeared. The reaction solution was extracted with dichloromethane(30 ml×3) and the organic layer was concentrated in vacuo. The resultingresidue was purified by column chromatographic separation(hexane/ethylacetate=1:1) to give 4 g of4-bromo-2-ethyl-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.NMR: δ0.91 (t, J=7.2 Hz, 3H), 1.52 (s, 3H), 1.95 (qd, J=7.2, 3.0 Hz,2H), 3.11 (s, 3H), 8.11 (d, J=8.7 Hz, 2H), 8.41 (d, J=8.7 Hz, 2H). IR(cm⁻¹): 2928, 1703, 1583, 1316, 1160, 552.

Step 6: Preparation of2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}4-phenyl-3(2H)-furanone

To a stirred solution of4-bromo-2-ethyl-2-methy-5-{4-(methysulfonyl)-phenyl}-3(2H)-furanone (200mg) in 15 ml of toluene, were added 40 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate solution, and 100 mg of benzeneboronic acid. The reactionsolution was stirred at reflux for 12 hours. Then the reaction solventwas evaporated under reduced pressure. The resulting residue wasextracted with water and dichloromethane (30 ml×3). The organic layerwas concentrated in vacuo. The resulting crude product mixture waspurified by column chromatography (hexane/ethylacetate=2:1) to give 60mg of2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone asa solid. mp: 115-117° C. NMR: δ0.96 (t, J=7.5 Hz, 3H), 1.55 (s, 3H),1.97 (q, J=7.5 Hz, 2H), 3.07 (s, 3H), 7.37 (m, 5H), 7.85 (d, J=8.7 Hz,2H), 7.93 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2928, 1697, 1620, 1403, 1318,1149, 959, 769, 552.

EXAMPLE 32

4-(3,5-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of4-bromo-2-ethyl-2-methy-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone(200 mg) in 15 ml toluene and 5 ml ethanol, were added 34 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate solution, and 110 mg of 3,5-difluorobenzeneboronic acid. Thenthe reaction solution was stirred at 95° C. for 12 hours. The reactionsolvent was evaporated off under reduced pressure and the resultingresidue was extracted with 50 ml water and dichloromethane (30 ml×3).The organic layer was concentrated in vacuo. The resulting crude productmixture was purified by column chromatography (hexane/ethylacetate=2:1)to obtain 80 mg of4-(3,5-difluorophenyl)-2-ethyl-2-methyl-5{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 122-124° C. NMR: δ0.95 (t, J=7.5 Hz, 3H), 1.54 (s, 3H),1.97 (m, 2H), 3.10 (s, 3H), 6.81 (m, 3H), 7.84 (d, J=8.7 Hz, 2H), 7.99(d, J=8.4 Hz, 2H). IR (cm⁻¹): 2975, 2928, 1698, 1627, 1321, 1150, 990,769, 552.

EXAMPLE 33

4-{3(N-Acetylamino)phenyl}-2-ethyl-2-methyl-5-}4(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of4-bromo-2-ethyl-2-methy-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone wascoupled with 120 mg of {(3-N-acetylamino)benzene}boronic acid accordingto a procedure similar to the synthetic procedure in Example 32 to yield120 mg of4-{(3-N-acetylamino)phenyl}-2-ethyl-2-methyl-5{4-(methylsulfonyl)phenyl}-3(2H)-furanone.mp: 56-57° C. NMR: δ0.95 (t, J=7.2, 3H), 1.54 (s, 3H), 1.95 (m, 2H),2.07 (s, 3H), 3.07 (s, 3H), 6.92 (m, 1H), 7.33 (m, 1H), 7.56 (m, 2H),7.85 (d, J=8.7 Hz, 2H), 7.93 (d, J=9.0 Hz, 2H), 8.00 (s, 1H). IR (cm⁻¹):3312, 3077, 2928, 2881, 1695, 1619, 1553, 1318, 1149, 958, 725, 641.

EXAMPLE 34

2-Ethyl-2-methyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

210 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone wasreacted with 170 mg of {4-(1-N-methylpyrazolyl)}-trimethylboronatelithium salt. Then the reaction solution was stirred at 90° C. for 12hours. The reaction solvent was evaporated off under reduced pressureand the resulting residue was diluted with 50 ml water. The aqueoussolution was then extracted with dichloromethane (30 ml×3) and theorganic layer was concentrated in vacuo. The resulting crude productmixture was purified by column chromatography (hexane/ethylacetate) togive 100 mg of2-ethyl-2methyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 78-80° C. NMR: δ0.92 (t, J=7.5 Hz, 3H), 1.59 (s, 3H).1.93 (m, 2H), 3.10 (s, 3H), 3.93 (s, 3H), 7.38 (d, J=0.6 Hz, 1H), 7.74(br s, 1H), 8.03 (m, 4H).

EXAMPLE 35

4-(4-Acetylphenyl)-2-ethyl-2-methyl-5-}4-(methylsulfonyl)phenyl)-3(2H)-furanoneStep 1: Preparation of2-ethyl-4-iodo-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To 8.88 g of2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone in 50 mlcarbon tetrachloride and 50 ml chloroform, were added[bis(trifluoroacetoxy)iodo]benzene (6.82 g) and iodine (4 g). Thereaction solution was stirred at room temperature for 4 hours. Then thereaction was quenched by adding saturated aqueous sodium thiosulfateuntil the characteristic color of iodine disappeared. The solution wasextracted with 50 ml water and dichloromethane (100 ml×3). The organiclayer was concentrated in vacuo and the resulting residue was purifiedby lo column chromatographic separation (hexane/ethylacetate=1:1) toyield 8.7 g of2-ethyl-4-iodo-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.NMR: δ0.89 (t, J=7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (q, J=7.5 Hz, 2H), 3.11(s, 3H), 8.11 (d, J=8.7 Hz, 2H), 8.34 (d, J=8.7 Hz, 2H). IR (cm⁻¹):2928, 1701, 1552, 1314, 1148, 747, 551.

Step 2: Preparation of4-(4-acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone

To a stirred solution of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200mg) in 15 ml toluene and 5 ml ethanol, were added 34 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2M aqueous sodiumcarbonate solution and 120 mg of 4-acetylbenzeneboronic acid. Then thereaction solution was stirred at 95° C. for 12 hours. The reactionsolvent was evaporated off under reduced pressure and the resultingresidue was extracted with 50 ml water and dichloromethane (30 ml×3).Then the organic layer was concentrated in vacuo and the resulting crudeproduct was purified by column chromatography (hexane/ethylacetate) toafford 120 mg of4-(4-acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 147-148° C. NMR: δ0.97 (t, J=7.5 Hz, 3H), 1.56 (s, 3H),1.99 (m, 2H), 2.62 (s, 3H), 3.08 (s, 3H), 7.39 (d, J=8.7 Hz, 2H), 7.83(d, J=8.7 Hz, 2H), 7.97 (m, 2H). IR (cm⁻¹): 2929, 1684, 1410, 1317,1149, 1016, 769, 552.

EXAMPLE 36

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone

To a stirred solution of4-bromo-2-ethyl-2-methy-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone(200 mg) in 15 ml toluene and 5 ml ethanol, were added 40 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of aqueous 2M sodiumcarbonate solution and 110 mg of (3-pyridyl)-trimethylboronate lithiumsalt. Then the reaction solution was stirred at 95° C. for 12 hours. Thereaction solvent was evaporated off under reduced pressure and theresulting residue was diluted with 50 ml water. The aqueous solution wasthen extracted with dichloromethane (30 ml×3) and the organic layer wasconcentrated in vacuo. The resulting crude product mixture was purifiedby column chromatography (hexane/ethylacetate) to obtain 35 mg of2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone.NMR: δ0.97 (t, J=7.5 Hz, 3H), 1.57 (s, 3H), 2.00 (m, 2H), 3.09 (s, 3H),7.37 (m, 1H), 7.71 (m, 1H), 7.83 (d, J=9.0 Hz, 2H), 7.98 (d, J=8.7 Hz,2H), 8.46 (s, 1H), 8.58 (s, 1H). IR (cm⁻¹): 3058, 2976, 1696, 1621,1401, 1318, 1149, 926, 769, 726, 552.

EXAMPLE 37

4-(4-t-Butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

150 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (150mg ) was coupled with 117 mg of (4-t-butylbenzene)boronic acid accordingto a procedure similar to the synthetic procedure for the Step 2 ofExample 35 to afford 100 mg of4-(4-t-butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone.mp: 45° C. NMR: δ0.95 (t, J=7.5 Hz, 3H), 1.33 (s, 9H), 1.54 (s, 3 H),1.96 (m, 2H), 3.08 (s, 3H), 7.38-7.41 (m, 2H), 7.86-7.95 (m, 4H). IR(cm⁻¹): 2967, 2871, 1696, 1594, 1320, 1149, 769, 552.

EXAMPLE 38

4-(3-Aminophenyl)-2-ethyl-2-methyl-5-{4-methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 110 mg of (3-aminobenzene)boronic acid by following aprocedure similar to the synthetic procedure in Step 2 of Example 35 toafford 105 mg of4-(3-aminophenyl)2-ethyl-2-methyl-5-{4-methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 77-78° C. NMR: d 0.94 (t, J=7.5 Hz, 3H), 1.53 (s, 3H),1.96 (m, 2H), 3.07 (s, 3H), 6.57 (m, 2H), 7.14 (m, 1H), 7.91 (m, 4H). IR(cm⁻¹): 3457, 3370, 2926, 1692, 1620, 1403, 1317, 1148, 959, 854, 769,552.

EXAMPLE 39

2-Ethyl-4-{4-(fluoromethyl)phenyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 110 mg of {4-(fluoromethyl)benzene}boronic acid accordingto a procedure similar to the procedure for the Step 2 of Example 35 toobtain 70 mg of2-ethyl-4-{4-(fluoromethyl)phenyl}-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone.NMR: δ0.96 (dt, J=7.5, 2.1 Hz, 3H), 1.55 (s, 3H), 1.97 (m, 2H), 3.07 (s,3H), 5.41 (d, J=23.9 Hz, 2H), 7.37 (m, 4H), 7.85 (m, 2H), 7.93 (m, 2H).IR (cm⁻¹): 2974, 2929, 1697, 1319, 1150, 769, 552.

EXAMPLE 40

4-{5-(2-Acetylthienyl)}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

200 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 100 mg of (2-acetylthiophene)-5-boronic acid by a proceduresimilar to the synthetic procedure in Step 2 of Example 35 to afford 70mg of4-{5-(2-acetylthienyl)}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.NMR: δ0.95 (t, J=7.2 Hz, 3H), 1.56 (s, 3H), 1.95 (m, 2H), 2.55 (s, 3H),3.13 (s, 3H), 7.21 (d, J=4.2 Hz, 1H), 7.95 (d, J=4.2 Hz, 1H), 7.85 (d,J=8.1 Hz, 2H), 8.08 (d, J=8.1 Hz, 2H). IR (cm⁻¹): 2926, 1690, 1315,1150, 772, 552.

EXAMPLE 41

2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(3-methylthienyl)}-3(2H)-furanone

200 mg of2-ethyl-4-iodo-2-methyl-5-4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 100 mg of {2-(3-methylthiophene)}-trimethylboronate lithiumsalt by following a procedure similar to the synthetic procedure inExample 36 to yield 150 mg of2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(3-methylthienyl)}-3(2H)-furanoneNMR: δ0.95 (t, J=7.5 Hz, 3H), 1.55 (s, 3H), 1.96 (s, 3H), 1.99 (m, 2H),3.06 (s, 3H), 6.80 (d, J=5.1 Hz, 1H), 7.36 (d, J=5.1 Hz, 1H), 7.91 (m,4H). IR (cm⁻¹): 2974, 2926, 1701, 1618, 1318, 1149, 770, 729, 552.

EXAMPLE 42

2-Ethyl-4-{3-(6-methoxypyridyl)}-2-methyl-5-{4(methylsulfonyl)phenyl}-3(2H)-furanone

150 mg of2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 98 mg of {3-(6-methoxypyridine)}trimethylboronate lithiumsalt according to a procedure similar to the synthetic procedure inExample 36 to yield 100 mg of2-ethyl-4-{3-(6-methoxypyridyl)}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 61° C. NMR: δ0.95 (t, J=7.5 Hz, 3H), 1.55 (s. 3H), 1.95(m, 2H), 3.08 (s, 3H), 3.95 (s, 3H), 6.78 (d, J=8.4 Hz, 1H), 7.53 (dd,J=8.4, 2.4 Hz, 1H), 7.85-7.88 (m, 2H), 7.95-7.98 (m, 2H), 8.04 (d, J=2.4Hz, 1H). IR (cm⁻¹): 2977, 2929, 1695, 1591, 1500, 1318, 1287, 1149,1021, 769, 552.

EXAMPLE 43

5-{4(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-phenyl-3(2H)-furanone Step1: Preparation of2-ethyl-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a stirred solution of2-ethyl-2-methyl-5-{(4-methylthio)phenyl}-3(2H)-furanone (6.0 g) in 50ml dichloromethane, was added dropwise at 0° C. 5.9 g of 70%m-chloroperoxybenzoic acid dissolved in 100 ml dichloromethane. Thereaction solution was stirred at 0° C. for 2 hours. Then the solvent wasremoved in vacuo, and the resulting residue was extracted with 100 mlwater and dichloromethane (50 ml×2). The organic layer was concentratedunder reduced pressure and the resulting crude product was purified bycolumn chromatography (hexane/ethylacetate=2: 1) to afford 4.5 g of2-ethyl-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone. NMR: δ0.89(t, J=7.5 Hz, 3H), 1.48 (s, 3H), 1.91 (m, 2H), 2.78 (s, 3H), 6.13 (s,1H), 8.07 (m, 4H).

Step 2: Preparation of2-ethyl-4-iodo-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

8.2 g of 2-ethyl-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone in200 ml carbon tetrachloride and 200 ml chloroform was mixed with 6.8 gof [bis(trifluoroacetoxy)iodo]benzene (BTI) and 4.1 g of iodine. Themixture was stirred at room temperature for 6 hours, followed byquenching the reaction by adding saturated aqueous sodium thiosulfateuntil the characteristic color of iodine disappeared. The quenchedsolution was extracted with 300 ml water and dichloromethane (200 ml×3).The organic layer was concentrated in vacuo and the resulting residuewas purified by column chromatography (hexane/ethylacetate=1:1) to give10.0 g of2-ethyl-4-iodo-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone.NMR: δ0.89 (t, J=7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (m, 2H), 2.73 (s, 3H),7.81 (d, J=8.7 Hz, 2H), 8.38 (d, J=8.7 Hz, 2H).

Step 3: Preparation of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone

8.0 g of2-ethyl-4-iodo-2-methyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone wasstirred in 50 ml trifluoroacetic anhydride (TFAA) at 0° C. for 3 hours.Then the volatile material was removed in vacuo, which was followed bytreatment with 30 ml of 1:1 methanol and triethylamine. The solvent wasremoved under reduced pressure. The same procedure of the treatment withmethanolic triethylamine and the solvent removal was repeated threetimes. Then the resulting residue was dissolved in 100 ml carbontetrachloride at 0° C., to which was added dropwise 5 ml of acetic acidsaturated with chlorine. The reaction solution was stirred at 0° C. for1 hour. The volatile materials including the unreacted chlorine wereevaporated off under reduced pressure. The resulting residue was mixedwith 100 ml THF and 20 ml ammonia water and the solution was stirred atroom temperature for 2 hours. Then the solvent was removed in vacuo andthe resulting residue was subjected to extraction with aqueous ammoniumacetate and ethylacetate. The ethylacetate layer was concentrated invacuo and the resulting crude product was purified by columnchromatography (hexane/ethylacetate=1:1) to obtain 2.0 g of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone. NMR:δ0.90 (t, J=7.5 Hz, 3H), 1.51 (s, 3H), 1.93 (m, 2H), 5.10 (br s, 2H),8.08 (d, J=8.7 Hz, 2H), 8.33 (d, J=8.7 Hz, 2H).

Step 4: Preparation of5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-phenyl-3(2H)-furanone

100 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone wasreacted with 90 mg of benzeneboronic acid by following a proceduresimilar to Step 2 of Example 35 to give 30 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-phenyl-3(2H)-furanone asa solid. mp: 153-154° C. NMR: δ0.95 (t, J=7.5 Hz, 3H), 1.54 (s, 3H),1.97 (m, 2H), 4.89 (br s, 2H), 7.26 (m, 2H), 7.36 (m, 3H), 7.79 (d,J=8.7 Hz, 2H), 7.90 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3340, 3256, 1684,1616, 1392, 1342, 1161.

EXAMPLE 44

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-thienyl)-3(2H)-furanone

100 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone wasreacted with 70 mg of (3-thiophene)boronic acid by following a proceduresimilar to the procedure in Step 2 of Example 35 to yield 20 mg of5-{4-(aminosulfonyl)phenyl)-2-ethyl-2-methyl-4-(3-thienyl)-3(2H)-furanoneas a solid. mp: 120-121° C. NMR: δ0.93 (t, J=7.5 Hz, 3H), 1.52 (s, 3H),1.95 (m, 2H), 5.08 (br s, 2H), 6.91 (dd, J=5.1, 1.8 Hz, 1H), 7.31 (dd,J=7.1, 3.0 Hz, 7.49 (dd, J=3.0, 1.8 Hz, 1H), 7.86 (d, J=8.7 Hz, 2H),7.96 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3345, 3252, 1682, 1616, 1343, 1158.MS (FAB) 364 (m+1).

EXAMPLE 45

4-(4-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone

100 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone wasreacted with 70 mg of (4-acetylbenzene )boronic acid by following aprocedure similar to the procedure in Step 2 of Example 35 to yield 15mg of4-(4-acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanoneas a solid. mp: 154-155° C. NMR: δ0.96 (t, J=7.5 Hz, 3H), 1.56 (s, 3H),1.98 (q, J=7.5 Hz, 2H), 2.62 (s, 3H), 4.95 (br s, 2H), 7.39 (d, J=8.7Hz, 2H), 7.77 (d, J=8.7 Hz, 2H), 7.93 (d, J=8.7 Hz, 2H), 7.95 (d, J=8.7Hz, 2H). IR (cm⁻¹): 3227, 1681, 1614, 1344, 1219, 1161. MS (FAB): 400(m+1).

EXAMPLE 46

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-fluoro-4-methoxyphenyl)-2-methyl-3(2H)-furanone

100 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone wasreacted with 80 mg of 3-fluoro-4-methoxybenzeneboronic acid by followinga procedure similar to the procedure for the Step 2 of Example 35 togive 25 mg of5-{4-(aminosulfonyl)phenyl}-2-ethyl-4-(3-fluoro-4-methoxyphenyl)-2-methyl-3(2H)-furanoneas a solid. mp: 113-114° C. NMR: δ0.94 (t, J=7.5 Hz, 3H), 1.53 (s, 3H),1.95 (q, J=7.5 Hz, 2H), 3.91 (s, 3H), 4.96 (br s, 2H), 6.99 (m, 3H),7.80 (d, J=8.4 Hz, 2H), 7.93 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3259, 1689,1608, 1517, 1270, 1159. MS (FAB): 406 (m+1).

EXAMPLE 47

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone Step 1:Preparation of 4-ethyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol

To a stirred solution of 3-ethyl-1-pentyn-3-ol (7.7 ml) in 300 mlanhydrous THF, was added dropwise 100 ml of 1.4 M methyllithium inhexane at −78° C. under argon. The mixture was further stirred for 30minutes, followed by dropwise addition of 4-(methylthio)benzaldehyde(9.3 ml). The reaction mixture was stirred for another 12 hours, duringwhich the cold bath was removed such that the reaction temperaturereached room temperature slowly. Then the reaction was quenched byadding dilute aqueous HCl. The solvent was removed in vacuo and theresulting residue was extracted with brine and dichloromethane (150ml×3). The organic layer was concentrated under reduced pressure and theresulting crude product was purified by recrystallization from hexaneand ethylacetate (4:1) to give 11.8 g of4-ethyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol as a low-meltingsolid. mp: 64-65° C. NMR: δ1.04 (t, J=7.5 Hz, 6H), 1.70 (q, J=7.5 Hz,4H), 2.49 (s, 3H), 5.47 (s, 1H), 7.26 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.4Hz, 2H). IR (cm⁻¹): 3368, 2970, 2207, 1637, 1589, 1262, 1093.

Step 2: Preparation of4-ethyl-4-hydroxy-1-{4-(methylthio)phenyl}-2-hexyn-1-one

To a stirred suspension of celite (20 g) and4-ethyl-1-{4-(methylthio)phenyl}-2-hexyn-1,4-diol (11 g) in 300 mldichloromethane, was added 25 g of pyridinium dichromate at 0° C. Thenthe reaction mixture was stirred for 12 hours at room temperature. Theinsoluble and metallic substances were removed by filtration throughFlorisil. The filtrate was extracted with dilute aqueous HCl anddichloromethane (150 ml×3). The organic layer was then washed with brineand dried over anhydrous magnesium sulfate. The organic layer wasconcentrated in vacuo and the resulting crude product was recrystallizedfrom 5:1 hexane and ethylacetate to yield 7.8 g of4-ethyl-4-hydroxy-1-{4-(methylthio)phenyl}-2-hexyn-1-one as alow-melting solid. mp: 49-50° C. NMR: δ1.12 (t, J=7.5 Hz, 6H), 1.83 (q,J=7.5 Hz, 4H), 2.15 (br s, 1H), 2.54 (s, 3H), 7.28 (d, J=8.7 Hz, 2H),8.02 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3432, 2970, 2208, 1636, 1588, 1285,1095.

Step 3: Preparation of2,2-diethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone

A solution 10 g of4-ethyl-4-hydroxy-1-{4-(methylthio)phenyl}-2-hexyn-1-one in 300 mlmethanol was stirred in the presence of 4 ml diethylamine at roomtemperature for 12 hours. Then the solvent was removed in vacuo and theresulting residue was extracted with dilute aqueous HCl anddichloromethane (50 ml×3). The organic layer was washed with brine andthen concentrated under reduced pressure to yield 5.6 g of2,2-diethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone. The crude productwas used for the next step without further purification. NMR: δ0.85 (t,J=7.5 Hz, 6H), 1.88 (q, J=7.5 Hz, 4H), 2.54 (s, 3H), 5.96 (s, 1H), 7.31(d, J=9.0 Hz, 2H), 7.75 (d, J=9.0 Hz, 2H). IR (cm⁻¹): 2971, 1690, 1597,1487, 1408, 1364, 1162, 1095.

Step 4: Preparation of2,2-diethyl-5-{4-(methylsulfonyl)phenyl}3(2H)-furanone

To a stirred solution of the crude2,2-diethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone (5.6 g) obtained inthe previous step in 50 ml TBF and 50 ml methanol, was added dropwise 20g of OXONE dissolved in 50 ml water at 0° C. Then the mixture was thenstirred at room temperature for 14 hours. The insoluble materials werefiltered off and the filtrate was concentrated in vacuo. The resultingresidue was extracted with water and ethylacetate (150 ml×2). Theethylacetate layer was concentrated and the resulting crude product waspurified by column chromatography (hexane/ethylacetate=2:1) to give 4.5g of 2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone as a solid.mp: 109-110° C. NMR: 0.86 (t, J=7.5 Hz, 6H), 1.91 (q, J=7.5 Hz, 4H),3.10 (s, 3H), 6.14 (s, 1H), 8.04 (d, J=9.0 Hz, 2H), 8.09 (d, J=9.0 Hz,2H). IR (cm⁻¹): 2973, 1695, 1588, 1561, 1408, 1315, 1152.

Step 5: Preparation of4-bromo-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To a stirred solution of2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (4.5 g) in 200ml chloroform with 3 ml acetic acid, was added dropwise 1.5 ml bromineat 0° C. The solution was then allowed to warm to room temperature andwas stirred for another 4 hours. The reaction was quenched by addingsaturated aqueous sodium thiosulfate until the characteristic color ofbromine disappeared. The reaction mixture was then extracted withdichloromethane (100 ml×2) and the organic layer was dried overanhydrous magnesium sulfate. After the magnesium sulfate was removed byfiltration, the filtrate was concentrated under reduced pressure. Theresulting crude product was purified by recrystallization from hexaneand ethylacetate to afford 4.5 g of4-bromo-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone. mp:130-131° C. NMR: δ0.88 (t, J=7.5 Hz, 6H), 1.95 (q, J=7.5 Hz, 4H), 3.11(s, 3H), 8.12 (d, J=8.7 Hz, 2H), 8.42 (d, J=8.7 Hz, 2H). IR (cm⁻¹):2973, 1705, 1583, 1558, 1315, 1160, 1084.

Step 6: Preparation of2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone

To a stirred solution of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (300mg) in 25 ml toluene and 10 ml ethanol, were added 40 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of aqueous 2M sodiumcarbonate solution and 140 mg of benzeneboronic acid. Then the reactionsolution was stirred at 95° C. for 12 hours. The reaction solvent wasevaporated off under reduced pressure and the resulting residue wasextracted with 50 ml water and dichloromethane (30 ml×3). The organiclayer was concentrated in vacuo and the resulting crude product mixturewas purified by column chromatography (hexane/ethylacetate) to give 130mg of 2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanoneas a solid. mp: 139-140° C. NMR: δ0.93 (t, J=7.5 Hz, 6H), 1.99 (q, J=7.5Hz, 4H), 3.07 (s, 3H), 7.24 (m, 2H), 7.37 (m, 3H), 7.86 (d, J=8.7 Hz,2H), 7.93 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2972, 1695, 1621, 1403, 1318,1149.

EXAMPLE 48

4-(3-Chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

300 mg of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 160 mg of (3-chlorobenzene)boronic acid according to aprocedure similar to the synthetic procedure of Step 6 of Example 47 toafford 160 mg of4-(3-chlorophenyl}-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid mp: 131-132° C. NMR: δ0.93 (t, J=7.5 Hz, 6H), 1.98 (q, J=7.5Hz, 4H), 3.08 (s, 3H), 7.12 (m, 1H), 7.30 (m, 3H), 7.85 (d, J=8.4 Hz,2H), 7.95 (d, J=8.4 Hz, 2H). IR (cm⁻¹): 2973, 1695, 1620, 1403, 1318,1150.

EXAMPLE 49

4-(4-Acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

300 mg of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 160 mg of (4-acetylbenzene)boronic acid according to aprocedure similar to the procedure of Step 6 of Example 47 to afford 80mg of4-(4-acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a foamy material. NMR: δ0.94 (t, J=7.5 Hz, 6H), 2.00 (q, J=7.5 Hz,4H), 2.62 (s, 3H), 3.11 (s, 3H), 7.39 (d, J=8.4 Hz, 2H), 7.86 (d, J=8.4Hz, 2H),7.97(dd, J=8.4, 1.5 Hz, 4H). IR (cm⁻¹): 2973, 1693, 1617, 1410,1317, 1151.

EXAMPLE 50

2,2-Diethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

300 mg of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wasreacted with 180 mg of (3-fluoro-4-methoxybenzene)boronic acid byfollowing a procedure similar to the synthetic procedure of Step 6 ofExample 47 to yield 100 mg of2,2-diethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanoneas a solid. mp: 183-184° C. NMR: δ0.92 (t, J=7.5 Hz, 6H), 1.97 (q, J=7.5Hz, 4H), 3.09 (s, 3H), 3.92 (s, 3H), 6.99 (m, 3H), 7.87 (d, J=8.7 Hz,2H), 7.96 (d, J=9.0 Hz, 2H). IR (cm⁻¹): 2972, 1694, 1518, 1317, 1149.

EXAMPLE 51

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone

300 mg of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone wascoupled with 130 mg of thiophene-3-boronic acid according to a proceduresimilar to the procedure of Step 6 of Example 47 to yield 80 mg of2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone asa foamy material. NMR: δ0.94 (t, J=7.5 Hz, 6H), 1.98 (q, J=7.5 Hz, 4H),3.10 (s, 3H), 6.91 (dd, J=5.4, 1.5 Hz, 1H), 7.33 (dd, J=5.1, 3.0 Hz,1H), 7.50 (dd, J=3.0, 1.2 Hz, 1H), 7.93 (d, J=8.7 Hz, 2H), 8.00 (d,J=8.7 Hz, 2H). IR (cm⁻¹): 2971, 1693, 1311, 1149.

EXAMPLE 52

2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone

To a stirred solution of4-bromo-2,2-diethyl-2-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (300mg) in 25 ml toluene and 10 ml ethanol, were added 40 mg oftetrakis(triphenylphosphine)palladium(0), 10 ml of aqueous 2M sodiumcarbonate solution and 130 mg of (3-pyridyl)-trimethylboronate lithiumsalt. Then the reaction solution was stirred at 95° C. for 12 hours. Thereaction solvent was evaporated off under reduced pressure and theresulting residue was extracted with 50 ml water and dichloromethane (30ml×3). Then the organic layer was concentrated in vacuo. The resultingcrude product mixture was purified by column chromatography(hexane/ethylacetate) to yield 30 mg of2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone asa foamy material. NMR: δ0.94 (t, J=7.5 Hz, 6H), 2.00 (q, J=7.5 Hz, 4H),3.09 (s, 3H), 7.36 (m, 1H), 7.54 (m, 1H), 7.84 (d, J=9.0 Hz, 2H), 7.98(d, J=8.7 Hz, 2H), 8.44 (d, J=1.8 Hz, 1H), 8.58 (dd, J=4.8, 1.8 Hz, 1H).IR (cm³¹ ¹): 2972, 1695, 1621, 1400, 1316, 1239, 1140.

EXAMPLE 53

2-{(4-Methylsulfonyl)phenyl}-3phenyl-1-oxa-spiro[4,4]non-2-en-4-one Step1 preparation of1-[3-hydroxy-3-(4-methylthiophenyl)-prop-1-ynyl]-cyclopentanol

To a stirred solution of 1-ethynyl-cyclopentan-1-ol (2.0 g) in 15 ml dryTHF at −78° C. under argon, was added 18 ml of 2.5 M butyllithium inhexane dropwise over 20 minutes. The reaction solution was stirred foranother 20 minutes, which was followed by the addition of4-methylthiobenzaldehyde (2.7 g) dropwlse. After stirring for another 2hours, the reaction was quenched by adding 20 ml of dilute aqueous HCl.The reaction solvent was removed in vacuo, and the resulting aqueoussolution was extracted with dichloromethane (30 ml×3). The organic layerwas concentrated under reduced pressure and the resulting residue waspurified by column chromatography (hexane/ethylacetate=1:1) to yield3.48 g of1-[3-hydroxy-3-{4-(methylthio)phenyl}-prop-1-ynyl]-cyclopentanol as asolid. mp: 118-120° C. NMR: δ0.73 (m, 4H), 1.87 (m, 4H), 2.16 (s, 1H),2.48 (s, 3H), 2.55 (s, 1H), 5.43 (d, J=5.7 Hz, 1H), 7.24(d, J=8.4 Hz,2H), 7.42 (d, J=8.4 Hz, 2H).

Step 2: Preparation of3-(1-hydroxy-cyclopentyl)-1-{4-(methylthio)}-propynone

To 1.54 g of1-[3-hydroxy-3-{4-(methylthio)phenyl}-prop-1-ynyl]-cyclopentanol in 20ml dichloromethane, were added 3.32 g of pyridinium dichromate and 3 gof celite. The suspension was stirred overnight at room temperature andthen the insoluble material was filtered off through Florisil. Thefiltrate was then subjected to column chromatography(hexane/ethylactate) to obtain 1.0 g of3-(1-hydroxy-cyclopentyl)-1-{4-(methylthio)phenyl}-propynone. NMR: δ1.85(m, 4H), 2.12 (m, 4H), 2.53 (s, 3H), 5.95 (s, 1H), 7.27 (m, 2H), 8.01(m, 2H).

Step 3: Preparation of2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one

1.54 g of 3-(1-hydroxy-cyclopentyl)-1-{4-(methylthio)phenyl}-propynonewas dissolved in 50 ml ethanol, added dropwise 0.75 ml diethylaminediluted with 50 ml ethanol. The reaction solution was stirred at roomtemperature for 4 hours, and then the solvent was removed in vacuo. Theresulting residue was extracted with 20 ml water and dichloromethane (30ml×3). Concentration of the organic layer was followed by columnchromatographic separation (hexane/ethylacetate) to give 858 mg of2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one. NMR: δ1.89 (m,6H), 1.92 (m, 2H), 2.47 (s, 3H), 5.89 (s, 1H), 7.24 (d, J=8.4 Hz, 2H),7.42 (d, J=8.7 Hz, 2H).

Step 4: Preparation of3-bromo-2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one

To 147 mg of 2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one in30 ml carbon tetrachloride, were added 1 ml bromine and 0.1 ml aceticacid. The reaction mixture was stirred for 1 hour at room temperature.Then the reaction was quenched by adding saturated aqueous sodiumthiosulfate solution until the characteristic color of brominedisappeared. The quenched solution was extracted with dichloromethane(10 ml×3). The organic layer was concentrated under reduced pressure andthe resulting residue was purified by column chromatography(hexane/ethylacetate) to yield 50 mg of3-bromo-2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one. NMR:δ1.98 (m, 4H), 2.11 (m, 4H), 2.55 (s, 3H), 7.32 (d, J=8.7 Hz, 2H), 8.13(d, J=8.7 Hz, 2H).

Step 5: Preparation of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one

50 mg of 3-bromo-2-{4-(methylthio)phenyl}-1-oxa-spiro[4,4]non-2-en-4-onewas stirred with 292 mg of OXONE at room temperature overnight in 5 mlethanol, 5 ml THF, and 5 ml water. Then the insoluble material wasfiltered off and the filtrate was concentrated under reduced pressure.The resulting aqueous layer was extracted with dichloromethane and theorganic layer was concentrated in vacuo. The resulting residue waspurified to column chromatography (hexane/ethylacetate) to afford 68 mgof 3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-oneas a solid. mp: 127-128° C. NMR: δ1.98 (m, 6H), 2.12 (m, 2H), 3.11 (s,3H), 8.09 (d, J=8.7 Hz, 2H), 8.37 (d, J=8.7 Hz, 2H).

Step 6: Preparation of2-{4-(methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,4]non-2-en-4-one

To a stirred solution of3-bromo-2-(4-(methylsulfonyl)phenyl)-1-oxa-spiro[4,4]non-2-en-4-one (77mg) in 5 ml of toluene and 15 ml ethanol, were added 15 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate solution, and 27 mg of benzeneboronic acid. Then the reactionsolution was stirred at 90° C. for 12 hours. The reaction solvent wasevaporated off under reduced pressure and the resulting residue wasextracted with 20 ml water and dichloromethane (30 ml×1). The organiclayer was concentrated in vacuo and the resulting crude product mixturewas purified by column chromatography (hexane/ethylacetate) to obtain 57mg of2-{4-(methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,4]non-2-en-4-one asa solid. mp: 184-185° C. NMR: δ2.09 (m, 6H), 2.17 (m, 2H), 3.06 (s, 3H),7.26 (m, 2H), 7,35 (m, 3H), 7.81 (d, J=8.1 Hz, 2H), 7.92 (d, J=8.1 Hz,2H). IR (cm⁻¹): 2925, 1695, 1591, 1403, 1150, 771.

EXAMPLE 54

3-(4-Isopropylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one

To a stirred solution of3-bromo-2-(4-methylsulfonylphenyl)-1-oxa-spiro[4,4]non-2-en-4-one (105mg) in 5 ml of toluene and 15 ml ethanol, were added 20 mg oftetrakis(triphenylphosphine)palladium(0), 5 ml of 2 M aqueous sodiumcarbonate solution, and 50 mg of 4-isopropylbenzeneboronic acid. Thereaction solution was stirred at 90° C. for 12 hours. The solvent wasremoved under reduced pressure and the resulting residue was extractedwith 20 ml water and dichloromethane (30 ml×3). The organic layer wasconcentrated in vacuo and the resulting crude product was purified bycolumn chromatography (hexane/ethylacetate) to obtain 87 mg of3-(4-isopropyl-phenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-oneas a solid. mp: 139-140° C. NMR: δ1.25 (s, 3H), 1.27 (s, 3H), 2.04 (m,6H), 2.15 (m, 2H), 2.92 (m, 1H), 3.06 (s, 3H), 7.21 (m, 4H), 7.83 (d,J=8.7 Hz, 2H), 7.93 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2960, 1694, 1622,1386, 1318, 1161, 768.

EXAMPLE 55

3-(4-Acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one

110 mg of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-one wascoupled with 55 mg of (4-acetylbenzene)boronic acid by following aprocedure similar to the synthetic procedure in Example 54 to give 93 mgof3-(4-acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,4]non-2-en-4-oneas a solid. mp: 126-130° C. NMR: δ2.04 (m, 6H), 2.17 (m, 2H), 2.61 (s,3H), 3.08 (s, 3H), 7.39 (d, J=8.4 Hz, 2H), 7.81 (d, J=8.4 Hz, 2H), 7.94(m, 4H). IR (cm⁻¹): 2963, 1689, 1317, 1150, 771.

EXAMPLE 56

2-{4(Methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,5]dec-2-en-4-one Step1: Preparation of1-[3-hydroxy-3-(methylthiophenyl)-prop-1-ynyl]-cyclohexan-1-ol

To a stirred solution of 1-ethynyl-cyclohexan-1-ol (3.2 g) in 80 ml dryTHF at −78° C. and under argon, was added dropwise 35 ml of 2.5 Mbutyllithium in hexane over 10 minutes. The reaction solution wasstirred for another 20 minutes, which was followed by the dropwiseaddition of 4-methylthiobenzaldehyde (3.2 ml). After stirred for another2 hours, the reaction was quenched by adding dilute aqueous HCl. Thereaction solvent was removed in vacuo, and the resulting aqueoussolution was extracted with dichloromethane. The organic layer wasconcentrated under reduced pressure and the resulting residue waspurified by column chromatography (hexane/ethylacetate) to yield 4.67 gof 1-[3-hydroxy-{4-(methylthio)phenyl}-prop-1-ynyl]-cyclohexanol. NMR:δ1.45 (m, 6H), 1.70 (m, 2H), 1.90 (m, 2H), 2.17 (d, 1H), 2.49 (s, 3H),3.57 (s, 1H), 5.48 (d, J=6.0 Hz 1H), 7.26 (d, J=8.4 Hz, 2H), 7.46 (d,J=8.4 Hz, 2H). IR (cm⁻¹): 3343, 2934, 1445, 1091.

Step 2: Preparation of3-(1-hydroxy-cyclohexyl)-1-{4-(methylthio)phenyl}-propynone

To 3.56 g of1-[3-hydroxy-{4-(methylthio)phenyl-prop-1-ynyl]-cyclohexanol dissolvedin 60 ml dichloromethane, was added 1.79 g of chromium oxide. Thereaction mixture was stirred overnight at room temperature, and then theinsoluble material was filtered off through Florisil. The filtrate wasconcentrated in vacuo and the resulting residue was purified by columnchromatography (hexane/ethylactate) to obtain 1.42 g of3-(1-hydroxy-cyclohexyl)-1-{4-(methylthio)phenyl}-propynone. NMR: δ1.56(m, 4H), 1.76 (m, 4H), 2.03 (m, 2H), 2.33 (s, 1H), 2.53 (s, 3H), 7.26(d, J=8.7 Hz, 2H), 8.01 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3416, 2936, 1637,1588, 1263, 1096.

Step 3: Preparation of2-{4-(methylthio)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one

1.3 g of 3-(1-hydroxy-cyclohexyl)-1-{4-(methylthio)phenyl}-propynone wasreacted with 0.6 ml diethylamine to obtain 858 mg of2-{4methylthio)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one by following aprocedure similar to the procedure in Step 3 of Example 53. NMR:δ1.62-1.82 (m, 10H), 2.54 (s, 3H), 5.92 (s, 1H), 7.30 (d, J=8.1 Hz, 2H),7.75 (d, J=8.4 Hz, 2H). IR (cm⁻¹): 2933, 1686, 1588, 1408, 1095, 744.

Step 4: Preparation of2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one

The 486 mg of 2-{4-(methylthio)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-onewas reacted with 1 g of OXONE by following a procedure similar to theprocedure in Step 4 of Example 53 to obtain 470 mg of2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one. NMR: δ1.77(m, 10H), 3.09 (s, 3H), 6.10 (s, 1H), 8.05 (m, 4H). IR (cm⁻¹): 2935,1694, 1589, 1408, 1315, 1153, 775.

Step 5: Preparation of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one

50 mg of 2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one wasreacted with bromine (0.5 ml) in the presence of 0.1 ml acetic acid toyield 68 mg of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one byfollowing a procedure similar to the procedure in Step 5 of Example 53.mp: 163-164° C. NMR: δ1.79 (m, 10H), 3.11 (s, 3H), 8.10 (d, J=8.1 Hz,2H), 8.40 (d, J=8.1 Hz, 2H). IR (cm⁻¹): 2936, 1709, 1583, 1316, 1149,912, 744.

Step 6: Preparation of2-{4-(methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,5]dec-2-en4-one

To 102 mg of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-onedissolved in 3 ml toluene and 15 ml ethanol, were added 16 mg oftetrakis(triphenylphosphin)palladium(0), 3 ml of 2 M aqueous sodiumcarbonate and 35 mg of benzeneboronic acid. The reaction mixture wasstirred at 90° C. for 12 hours. The reaction mixture was then purifiedby a procedure similar to the procedure in Step 6 of Example 53 toafford 50 mg of2-{4-(methylsulfonyl)phenyl}-3-phenyl-1-oxa-spiro[4,5]dec-2-en-4-one asa solid. mp: 126-127° C. NMR: δ1.77-1.85 (m, 10H), 3.06 (s, 3H), 7.27(m, 2H), 7.35 (m, 3H), 7.83 (d, J=8.1 Hz, 2H), 7.94 (d. J=8.1 Hz, 2H).IR (cm⁻¹): 2936, 1693, 1621, 1404, 1318, 1147, 1129, 730.

EXAMPLE 57

3-(4-Acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-2-en-4-one

To 84 mg of3-bromo-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-onedissolved in 3 ml toluene and 15 ml ethanol, were added 15 mg oftetrakis(triphenylphosphin)palladium(0), 3 ml of 2 M aqueous sodiumcarbonate and 40 mg of (4-acetylbenzene)boronic acid. The reactionmixture was stirred at 90° C. for 12 hours. The reaction mixture wasthen purified according to a procedure similar to Step 6 of Example 56to obtain 35 mg of3-(4-acetylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one.NMR: δ1.78-1.86 (m, 10H), 2.61 (s, 3H), 3.08 (s, 3H), 7.37 (d, J=8.4 Hz,2H), 7.84 (d, J=8.4 Hz, 2H), 7.97 (m, 4H). IR (cm⁻¹): 2963, 1689, 1621,1317, 1150, 771.

Compounds of Example 58˜Example 103 were synthesized by following aprocedure similar to the synthetic procedure in Example 2.

EXAMPLE 58˜EXAMPLE 103

Example R Melting point & spectral data 58 4-F mp: 154-155° C. NMR: δ1.56(s, 6H), 3.11(s, 3H), 7.09(m, 2H), 7.30(m, 2H), 7.83(d, J=8.4Hz,2H), 7.95(d, J=8.4Hz, 2H). IR(cm⁻¹): 2930, 1696, 1621, 1591, 1386, 1283,1149, 1090, 1051, 840, 749. MS(EI): 360(m). 59 4-Cl Mp: 153-154° C. NMR:δ 1.57(s, 6H), 3.08(s, 3H), 7.23(d, J=8.1Hz, 2H), 7.31(d, J=8.1Hz, 2H),7.83(d, J=8.1Hz, 2H), 7.97(d, J=8.1Hz, 2H). IR(cm⁻¹): 2928, 1696, 1620,1384, 1160, 1090, 770, 551. MS(EI): 376(m). 60 3-Cl, mp: 171-173° C.NMR: δ 1.58(s, 6H), 3.09(s, 3H), 4-Cl 7.10(dd, J=8.4, 1.8Hz, 1H),7.44(m, 2H), 7.83(d, J=8.7Hz, 2H), 7.98(d, J=8.7Hz, 2H). IR(cm⁻¹): 1693,1620, 1317, 1150. 61 4-Et mp: 95-97° C. NMR: δ 1.26(t, J=7.5Hz, 3H),1.58 (s, 6H), 2.68(q, J=7.2Hz, 2H), 3.09(s, 3H), 7.21(m, 4H), 7.90(m,4H). IR(cm⁻¹): 1697, 1594, 1386, 1318, 1241, 1149, 912, 744. 62 3-Cl mp:151-152° C. NMR: δ 1.58(s, 6H), 3.08(s, 3H), 7.14(m, 1H), 7.33(m, 3H),7.83(d, J=8.7Hz, 2H), 7.95(d, J=8.4Hz, 2H). IR(cm⁻¹): 3020, 2982, 1698,1619, 1384, 1240, 1150, 958, 753. 63 3-CH₃ mp: 140-141° C. NMR: δ1.57(s, 6H), 2.35(s, 3H), 3.07(s, 3H), 7.02(d, J=7.5Hz, 1H), 7.15(m,2H), 7.26(d, J=7.5Hz, 1H), 7.85(d, J=8.7Hz, 2H), 7.92(d, J=8.7Hz, 2H).IR(cm⁻¹): 2928, 1697, 1403, 1318, 1056, 956, 768. 64 2-OMe mp: 109-111°C. NMR: δ 1.58(s, 6H), 3.04(s, 3H), 3.54(s, 3H), 6.90-6.93(m, 1H),7.00-7.06(m, 1H), 7.22-7.25(m, 1H), 7.40-7.42(m, 1H), 7.79-7.82(m, 2H),7.88-7.91(m, 2H). IR(cm⁻¹): 3014, 1697, 1590, 1403, 1318, 1251, 1150,960. 65 2-F mp: 120-122° C. NMR: δ 1.60(s, 6H), 3.06(s, 3H),7.06-7.14(m, 1H), 7.20-7.14(m, 1H), 7.31-7.43(m, 2H), 7.80-7.83(m, 2H),7.91-7.95(m, 2H). IR(cm⁻¹): 2982, 1699, 1596, 1404, 1318, 1150, 961,761. 66 3-NH₂ mp: 186-187° C. NMR: δ 1.56(s, 6H), 3.06(s, 3H), 3.69(s,2H), 6.57(d, J=7.5Hz, 1H), 6.66(m 2H), 7.14(t, J=7.8Hz, 1H), 7.87(d,J=9.0Hz, 2H), 7.92(d, J=8.7Hz, 2H). IR(cm⁻¹): 3460, 3368, 1693, 1619,1403, 1316, 1219, 1148, 958. 67 3- mp: 169-170° C. NMR: δ 1.57(s, 6H),3.07(s, 3H), OMe, 3.82(s, 3H), 3.91(s, 3H), 6.83(m, 3H), 7.89(d, 3-OMeJ=9.0Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 3017, 2932, 1698, 1592,1515, 1403, 1318, 1250, 1025, 760. 68 2- mp: 107-108° C. NMR: δ 1.56(s,6H), 3.04(s, 3H), OMe, 3.51(s, 3H), 3.85(s, 2H), 6.48(d, J=2.4Hz, 1H),6.58 4-OMe (d, J=8.4Hz, 1H), 7.15(d, J=8.7Hz, 1H), 7.89(d, J=8.7Hz, 2H),7.93(d, J=9.0Hz, 2H). IR(cm⁻¹): 1699, 1403, 1318, 1150, 1072, 755. 692-Cl mp: 100-103° C. NMR: δ 1.61(s, 6H), 3.05(s, 3H), 7.25-7.27(m, 1H),7.34-7.38(m, 2H), 7.47-7.52 (m, 1H), 7.73-7.76(m, 2H), 7.89-7.92(m, 2H).IR(cm⁻¹): 1699, 1403, 1318, 1150, 1072, 755. 70 2-CH₃ mp: 130-131° C.NMR: δ 1.59(s, 6H), 2.12(s, 3H), 3.04(s, 3H), 7.07-7.09(m, 1H),7.20-7.24(m, 1H), 7.31-7.33(m, 2H), 7.73-7.76(m, 2H), 7.87-7.90(m, 2H).IR(cm⁻¹): 1697, 1403, 1318, 1149, 960, 754. 71 4-CF₃ mp: 144-146° C.NMR: δ 1.60(s, 6H), 3.09(s, 3H), 7.41-7.43(m, 2H), 7.63-7.65(m, 2H),7.81-7.84(m, 2H), 7.96-7.98(m, 2H). IR(cm⁻¹): 1698, 1632, 1325, 1125,1068, 959, 770. 72 4- mp: 137-141° C. NMR: δ 1.57(s, 6H), 2.51(s, 3H),SCH₃ 3.08(s, 3H), 7.17-7.22(m, 2H), 7.24-7.27(m, 2H), 7.82-7.88(m, 2H),7.93-7.96(m, 2H). IR(cm⁻¹): 1698, 1316, 1149, 1092, 960, 770. 73 H mp:192-193° C. NMR: δ 1.58(s, 6H), 3.07(s, 3H), 7.27(m, 2H), 7.36(m, 3H),7.84(d, J=8.7Hz, 2H), 7.93(d, J=8.4Hz, 2H). IR(cm⁻¹): 1697, 1503, 1404,1245, 1148, 959, 770. 74 2-Cl, mp: 77-78° C. NMR: δ 1.60(s, 6H), 3.05(s,3H), 4-Cl 7.20(d, J=8.1Hz, 1H), 7.34(dd, J=8.4, 2.4Hz, 1H), 7.51(d,J=1.8Hz, 1H), 7.74(d, J=8.7Hz, 2H), 7.94(d, J=8.7Hz, 2H). IR(cm⁻¹):2929, 1701, 1623, 1404, 1318, 1150, 960, 770. 75 3-Cl, mp: 187-188° C.NMR: δ 1.58(s, 6H), 3.09(s, 3H), 5-Cl 7.19(d, J=1.8Hz, 2H), 7.35(t,J=1.8Hz, 1H), 7.83(d, J=8.7Hz, 2H), 7.99(d, J=8.7Hz, 2H). IR(cm⁻¹):3019, 1697, 1616, 1318, 1245, 1151, 958, 770. 76 4-t-Bu mp: 142-143° C.NMR: δ 1.33(s, 9H), 1.57(s, 6H), 3.07(s, 3H), 7.19-7.22(m, 2H),7.38-7.41(m, 2H), 7.86-7.95(m, 4H). IR(cm⁻¹): 2964, 1698, 1594, 1319,1150, 1107, 960, 770. 77 4-Ph mp: 150-153° C. NMR: δ l.60(s, 6H),3.07(s, 3H), 7.35-7.38(m, 3H), 7.43-7.48(m, 2H), 7.61-7.64(m, 4H),7.89-7.97(m, 4H). IR(cm⁻¹): 1696, 1593, 1384, 1149, 1054, 959, 755. 784-Br mp: 159-161° C. NMR: δ 1.57(s, 6H), 3.08(s, 3H), 7.15-7.18(m, 2H),7.50-7.53(m, 2H), 7.82-7.85(m, 2H), 7.94-7.97(m, 2H). IR(cm⁻¹): 1697,1620, 1383, 1318, 1150, 1012, 770. 79 4- mp: 130-135° C. NMR: δ 1.60(s,6H), 3.09(s, 3H), CHO 7.47-7.50(m, 2H), 7.81-7.84(m, 2H), 7.88-7.91(m,2H), 7.95-7.98(m, 2H), 10.03(s, 1H). IR(cm⁻¹): 1698, 1617, 1385, 1317,1149, 960, 770. 80 3-F, mp: 162° C. NMR: δ 1.58(s, 6H), 3.09(s, 3H), 4-F6.99(m, 1H), 7.16(m, 2H), 7.83(d, J=9.0Hz, 2H), 7.98(d, J=8.7Hz, 2H).IR(cm⁻¹): 1698, 1597, 1515, 1384, 1210, 1149, 958, 770. 81 2-F, mp:181-182° C. NMR: δ 1.59(s, 6H), 3.07(s, 3H), 4-F 6.87(m, 1H), 7.00(m,1H), 7.33(m, 1H), 7.81(d, J=9.0Hz, 2H), 7.95(d, J=9.0Hz, 2H). IR(cm⁻¹):1699, 1593, 1403, 1319, 1151, 1097, 972, 770. 82 3-F, mp: 144-145° C.NMR: δ 1.60(s, 6H), 3.08(s, 3H), 4-OMe 3.95(s, 3H), 6.92(m, 3H), 7.88(d,J=8.7Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 1695, 1611, 1516, 1316,1270, 1123, 1023, 858, 769. 83 3-F, mp: 139-141° C. NMR: δ 1.57(s, 6H),2.28(s, 3H), 4-Me 3.07(s, 3H), 6.99-7.02(m, 2H), 7.13-7.16(m, 1H),7.82-7.86(m, 2H), 7.92-7.95(m, 2H). IR(cm⁻¹): 1698, 1623, 1588, 1503,1319, 1253, 1149, 756. 84 4-iso- mp: 121-123 ° C. NMR: δ 1.26(s, 3H),1.28(s, 3H), Pr 2.89-2.99(m, 1H), 3.07(s, 3H), 7.18-7.26(m, 4H),7.85-7.94(m, 4H). IR(cm⁻¹): 2962, 1697, 1594, 1402, 1319, 1240, 1150,770. 85 3-Me, mp: 155-156° C. NMR: δ 1.56(s, 6H), 2.25(s, 3H), 4-Me2.28(s, 3H), 3.06(s, 3H), 6.96(dd, J=7.8, 1.8Hz, 1H), 7.08(s, 1H),7.13(d, J=7.8Hz, 1H), 7.76(d, J=9.0Hz, 1H), 7.92(d, J=9.0Hz, 2H).IR(cm⁻¹): 1698, 1594, 1403, 1318, 1250, 1149, 856, 770. 86 3-iso- mp:83-84° C. NMR: δ 1.19(s, 3H), 1.21(s, 3H), Pr 1.58(s, 6H), 2.88(m, 1H),3.06(s, 3H), 7.10(m, 2H), 7.21(m, 1H), 7.31(t, J=7.8Hz, 1H), 7.76(d,J=9.0Hz, 2H), 7.92(d, J=8.7Hz, 2H). IR(cm⁻¹): 1697, 1618, 1384, 1318,1149, 957, 770. 87 3-CF₃, mp: 168° C. NMR: δ 1.61(s, 6H), 3.07(s, 3H),5-CF₃ 7.76(s, 2H), 7.80(d, J=8.4Hz, 2H), 7.84(s, 1H), 8.00(d, J=8.4Hz,2H). IR(cm⁻¹): 1701, 1593, 1405, 1321, 1250, 770. 88 4-SEt mp: 103-105°C. NMR: δ 1.33-1.38(t, J=7.2Hz, 3H), 1.57(s, 6H), 2.94-3.02(q, J=7.5Hz,2H), 3.08 (s, 3H), 7.18-7.21(m, 2H), 7.29-7.32(m, 2H), 7.84-7.87(m, 2H),7.92-7.95(m, 2H). IR(cm⁻¹): 1695, 1588, 1384, 1318, 1149, 770. 89 3,4,5-mp: 90-100° C. NMR: δ 1.58(s, 6H). 3.06(s, 3H), tri- 3.76(s, 6H),3.88(s, 3H), 7.88-7.97(m, 4H), 8.04- OMe 8.06(m, 2H). IR(cm⁻¹): 1693,1584, 1391, 1321, 1125, 958. 90 5-iso- mp: 128-129° C. NMR: δ 1.22(m,6H), 1.58(s, Pr, 6H), 3.03(s, 3H), 3.51(s, 3H), 6.82-6.85(m, 1H), 2-OMe7.08(m, 1H), 7.19-7.23(m, 1H), 7.80-7.83(m, 2H), 7.87-7.90(m, 2H).IR(cm⁻¹): 2960, 1700, 1502, 1318, 1149, 771. 91 3- mp: 75-80° C. NMR: δ1.60(s, 6H), 3.08(s, 3H), CHO 7.55-7.58(m, 2H), 7.80-7.84(m, 4H),7.93-7.96 (m, 2H), 10.01(s, 1H). IR(cm⁻¹): 2929, 1696, 1621, 1589, 1403,1149, 771. 92 2- mp: 70-80° C. NMR: δ 1.63(s, 6H), 3.04(s, 3H), CHO7.61-7.62(m, 2H), 7.71-7.74(m, 2H), 7.88-7.91(m, 2H), 8.03-8.04(m, 2H),9.94(s, 1H). IR(cm⁻¹): 1696, 1592, 1405, 1316, 1150, 960, 772. 93 2-CF₃mp: 61-62° C. NMR: δ 1.59(s, 6H), 3.03(s, 3H), 7.29(m, 1H), 7.57(m, 2H),7.68(m, 2H), 7.82(d, J=8.7Hz, 2H), 7.87(d, J=8.7Hz, 2H). IR(cm⁻¹): 1702,1404, 1316, 1128. 94 5-F, mp: 159-160° C. NMR: δ 1.58(s, 6H), 2.35(s,3H), 2-CH₃ 3.06(s, 3H), 6.96(m, 1H), 7.15(m, 2H), 7.28(m, 1H), 7.82(dd,J=8.4, 1.8Hz, 2H), 7.91(dd, J=6.6, 1.8Hz, 2H). IR(cm⁻¹): 1701, 1594,1404, 1319, 1160. 95 3-OMe mp: 151-l52° C. NMR: δ 1.58(s, 6H), 3.07(s,3H), 3.79(s, 3H), 6.83(m, 2H), 6.90(m, 1H), 7.29(m, 1H), 7.85(d,J=8.7Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 1696, 1620, 1385, 1318,1261, 1148. 96 4-n-Pr mp: 99-100° C. NMR: δ 0.96(t, J=7.2Hz, 3H), 1.59(s, 6H), 1.66(q, J=7.5Hz, 2H), 2.61(t, J=7.8Hz, 2H), 3.07(s, 3H),7.19(s, 4H), 7.89(dd, J=8.7, 8.7Hz, 4H). IR(cm⁻¹): 1698, 1594, 1382,1318, 1244, 1149. 97 4-n-Bu mp: 84-85° C. NMR: δ 0.83(t, J=7.5Hz. 3H),1.26(m, 4H), 1.58(s, 6H), 2.61(t, J=7.5Hz, 2H), 3.06(s, 3H), 7.18(m,4H), 7.87(m, 4H). IR(cm⁻¹): 1698, 1594, 1382, 1318, 1244, 1149. 98 4-NMR: δ 1.55(s, 6H), 2.98(s, 6H), 3.07(s, 3H), 6.72 NMe₂ (d, J=8.7Hz,2H), 7.14(d, J=9.0Hz, 2H), 7.91(m, 4H). 99 3- mp: 98° C. NMR: δ 1.59(s,6H), 3.07(s, 3H), 6.63 CHF₂ (t, J=56Hz, 1H), 7.26(m, 1H), 7.44(m, 3H),7.81(m, 2H), 7.95(m, 2H). IR(cm⁻¹): 1699, 1622, 1403, 1318, 1150. 1004-Cl, mp: 153-154° C. NMR: δ 1.57(s, 6H), 3.09(s, 3H), 3-F 7.00(m, 1H),7.13(m, 1H), 7.39(t, J=7.8Hz, 1H), 7.84(m, 2H), 7.97(m, 2H). IR(cm⁻¹):1699, 1622, 1403, 1318, 1150. 101 4-F, mp: 144-146° C. NMR: δ 1.58(s,6H), 2.11(s, 3H), 2-CH₃ 3.06(s, 3H), 7.28(m, 1H), 7.36(m, 2H), 7.73(d,J=9.0Hz, 2H), 7.82(d, J=8.7Hz, 2H). 102 4- mp: 132-133° C. NMR: δ1.58(s, 6H), 3.07(s, 3H), CH₂F 5.39(d, J=47.7Hz, 2H), 7.26(m, 4H),7.85(m, 2H), 8.01(m, 2H). IR(cm⁻¹): 1696, 1623, 1386, 1318, 1182, 1072103 2-F, mp: 141-142° C. NMR: δ 1.59(s, 6H), 3.08(s, 3H), 5-F 7.03(m,3H), 7.83(d, J=8.7Hz, 2H), 7.92(d, J=8.7Hz, 2H). IR(cm⁻¹): 1696, 1212,913.

EXAMPLE 104

2,2-Dimethyl-4-(4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

30 mg of2,2-dimethyl-4-(4methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone(Example 3) in 30 ml dichloromethane was stirred with 0.1 ml borontribromide (1.0 M solution in CH₂Cl₂) at room temperature for 4 hours.And then 10 ml aqueous sodium thiosulfate was added to the reactionmixture. The mixed solution was concentrated in vacuo and was extractedwith 50 ml water and dichloromethane (50 ml×3). The organic layer wasconcentrated under reduced pressure and was purified by columnchromatography (ethylacetate) to afford 25 mg of2,2-dimethyl-4-(4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.mp: 150-152° C. NMR: δ1.56 (s, 6H), 2.77 (s, 1H), 3.07 (s, 3H), 6.81 (d,J=8.7 Hz, 2H), 7.14 (d, J=8.7 Hz, 2H), 7.90 (m, 4H). IR (cm⁻¹): 3492,2929, 1696, 1597, 1393, 1151, 914, 744.

Compounds of Example 105 and Example 107 were prepared from thecorresponding methoxy compounds by following procedures similar to thesynthetic procedure of Example 104.

EXAMPLE 105˜EXAMPLE 107

Example R Melting point & spectral data 105 2-OH mp: 182-183° C. NMR: δ1.62(s, 6H), 3.08(s, 3H), 6.75-6.81(m, lH), 6.87-6.91(m, 1H),7.04-7.08(m, 1H), 7.47(s, 1H), 7.84-7.87(m, 2H), 7.93-7.96(m, 2H).IR(cm⁻¹): 3384, 1695, 1590, 1406, 1317, 1145, 961, 757. 106 2-OH, mp:183-184° C. NMR: δ 1.61(s, 6H), 3.08(s, 3H), 4-OMe 3.80(s, 3H), 6.37(dd,J=8.7, 2.7Hz, 2H), 6.60(d, J=3.0Hz, 1H), 6.76(d, J=8.4Hz, 1H), 7.82(s,1H), 7.87(d, J=8.7Hz, 2H), 7.95(d, J=9.0Hz, 2H). IR(cm⁻¹): 3371, 1697,1591, 1405, 1317, 1296, 1140, 961, 771. 107 4-OH, mp: 230-231° C. NMR: δ1.57(s, 6H), 3.08(s, 3H), 3-F 6.90(m, 1H), 6.97(d, J=8.7Hz, 1H),7.07(dd, J=11.4, J=4.8Hz, 2H), 7.85(d, J=8.7Hz, 2H), 7.95 (d, J=8.7Hz,2H).

EXAMPLE 108

4-{3-(Acetylamino)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

To 20 mg of4-(3-aminophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone(Example 66) in 10 ml dry dichlorometane, was added 0.3 ml aceticanhydride at 0° C., and the solution was stirred at room temperature foran hour. Then the reaction mixture was concentrated in vacuo, and wasextracted with water and dichloromethane. The organic layer wasconcentrated in vacuo and was purified by column chromatography(hexane/ethylacetate=2:1) to give 15 mg of4-{3-N-(acetylamino)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.mp: 217-218° C. NMR: δ1.55 (s, 6H), 2.11 (s, 3H), 3.05 (s, 3H), 6.96 (d,J=7.5 Hz, 1 ), 7.31 (d, J=8.1 Hz, 1H), 7.40 (s, 1H), 7.49 (d, J=8.1 Hz),7.84 (d, J=8.4 Hz, 2H), 7.91 (d, J=8.4 Hz, 2H). IR (cm⁻¹): 3341, 1690,1424, 1316, 1149, 959, 770.

EXAMPLE 109

2,2-Dimethyl-4,5-di{4-(methylsulfonyl)phenyl}-3(2H)-furanone

50 mg of2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(methylthio)-phenyl}-3(2H)-furanone(Example 72) in 10 ml dichloromethane and 2 ml methanol was stirred with300 mg of OXONE at room temperature for 4 hours. The insoluble materialwas filtered off and the filtrate was washed with aqueous sodiumbicarbonate. The organic layer was then concentrated under reducedpressure and was purified by column chromatography (ethylacetate) togive 45 mg of2,2-dimethyl-4,5-di{4-(methylsulfonyl)phenyl}-3(2H)-furanone. mp:245-257° C. NMR: δ1.60 (s, 6H), 3.08 (s, 3H), 3.10 (s, 3H), 7.50-7.53(m, 2H), 7.79-7.82 (m, 2H), 7.94-8.00 (m, 4H). IR (cm⁻¹): 2931, 1698,1510, 1387, 1258, 1150, 960, 846, 770.

EXAMPLE 110

2,2-Dimethyl-4-{4-(ethylsulfonyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

100 mg of2,2-dimethyl-4-{4-(ethylthio)phenyl}-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone(Example 88) in 10 ml dichloromethane, 2 ml methanol was stirred with400 mg of OXONE at room temperature for 12 hours. The insoluble materialwas filtered off and the filtrate was washed with aqueous sodiumbicarbonate. The organic layer was then concentrated under reducedpressure and was purified by column chromatography (ethylacetate) togive 70 mg of2,2-dimethyl-4-{4-(ethylsulfonyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.mp: 198-203° C. NMR: δ1.29-1.34 (t, J=7.2 Hz, 3H), 1.60 (s, 6H), 3.10(s, 3H), 3.10-3.18 (q, J=7.5 Hz, 2H), 7.49-7.52 (m, 2H), 7.79-7.82 (m,2H), 7.90-7.93 (m, 2H), 7.97-7.99 (m, 2H). IR (cm⁻¹): 1697, 1619, 1384,1315, 1150, 960, 770.

EXAMPLE 111

2,2-Dimethyl-4-{4-(1-hydroxyethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone

A mixture of4-(4-acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone(150 mg, Example 10), sodium borohydride(35mg) and cerium(III) chloride(20 mg) in 40 ml methaol was stirred at room temperature for 12 hours,which was followed by addition of water. Then the methanol was removedin vacuo and the resulting aqueous solution was extracted withethylacetate. The ethylacetate layer was concentrated under reducedpressure and was purified by column chromatography(hexane/ethylacetate=1:1) to obtain 100 mg of2,2-dimethyl-4-{4-(1-hydroxyethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone.NMR: δ1.51-1.53 (d, J=6.3 Hz, 3H), 1.58 (s, 6H), 3.07 (s, 3H), 4.90-4.97(q, J=6.3 Hz, 1H), 7.25-7.28 (m, 2H), 7.39-7.42 (m, 2H), 7.84-7.86 (m,2H), 7.92-7.95 (m, 2H). IR (cm⁻¹): 3502, 2977, 1696, 1594, 1317, 1149960, 771.

Compounds of Example 112˜Example 124 were prepared accordin toprocedures similar to the procedure employed for the synthesis ofExample 15.

EXAMPLE 112˜EXAMPLE 124

Example AR Melting point & spectral data 112 2-Naphthyl mp: 174-175° C.NMR: δ 1.62(s, 6H), 3.06(s, 3H), 7.24-7.28(m, 1H), 7.49-7.52(m, 2H),7.81-7.92(m, 8H). IR(cm⁻¹): 1695, 1589, 1403, 1318, 1148, 957, 770. 1132-Thienyl NMR: δ 1.58(s, 6H), 3.09(s, 3H), 7.05-7.07 (m, 1H),7.11-7.13(m, 1H), 7.35-7.37(m, 1H), 7.97-7.98(m, 4H). 114 2-(5- mp:134-135° C. NMR: δ 1.59(s, 6H), 2.55(s, Acetyl)- 3H), 3.12(s, 3H),7.21(d, J=3.6Hz, 1H), 7.62(d, thienyl J=3.9Hz, 1H), 7.93(m, 2H), 8.05(m,2H). IR (cm⁻¹): 2928, 1703, 1658, 1450, 1316, 1274, 1150, 771. 1154-Pyridyl NMR: δ 1.60(s, 6H), 3.10(s, 3H), 7.76(m, 1H), 7.82(m, 2H),7.80(m, 3H), 8.63(m, 2H). 116 3-(6- mp: 63-64° C. NMR: δ 1.58(s, 6H), 308(s, Methoxy- 3H), 3.95(s, 3H), 6.78(d, J=8.7Hz, 1H), 7.52 pyridyl) (m,1H). 7.84(m, 2H), 7.95(m, 2H), 8.05(m, 1H). IR(cm⁻¹): 1697, 1591, 1288,1150, 1023, 771, 552. 117 4-(1-N- mp: 143-145° C. NMR: δ 1.45(m, 6H),1.52(s, isopropyl- 6H), 3.10(s, 3H), 4.32(m, 1H), 7.11(s, 1H),pyrazolyl) 7.16(s, 1H), 8.05(m, 4H). IR(cm⁻¹): 2981, 2931, 1698, 1561,1409, 1315, 1152, 967, 775, 552. 118 3-(6- mp: 100° C. NMR: δ 1.59(s,6H), 2.59(s, 3H), Methyl- 3.08(s, 3H), 7.21(d, J=8.1Hz, 1H), 7.59(m,pyridyl) 1H), 7.82(m, 2H), 7.95(m, 2H), 8.34(d, J=2.1Hz, 1H). 119 2-(5-mp: 198-199° C. NMR: δ 1.63(s, 6H), 2.62(s, Formyl-4- 3H), 3.07(s, 3H),7.82(m, 2H), 7.99(m, 2H), methyl- 8.18(m, 1H), 10.05(s, 1H). IR(cm⁻¹):2928, thienyl) 1704, 1658, 1618, 1316, 1215, 1150, 771. 120 2-{5-(2 mp:118-120° C. NMR: δ 1.48(m, 2H), 1.57(s, [1,3]- 6H), 3.11(s, 3H), 4.02(m,2H), 4.28(m, 2H), Dioxalonyl)- 5.71(s, 1H), 7.08(m, 2H), 7.98(s, 4H). IRthienyl} (cm⁻¹): 2977, 2927, 2857, 1702, 1378, 1317, 1149, 1094, 766.121 2-(5- mp: 168-170° C. NMR: δ 1.60(s, 6H), 3.15(s, Formyl- 3H),7.31(d, J=3.9Hz, 1H), 7.70(d, J=3.9Hz, thienyl) 1H), 7.97(m, 2H),8.07(m, 2H), 9.89(s, 1H). IR (cm⁻¹): 2980, 2928, 1703, 1683, 1589, 1453,1316, 1226, 1150. 122 2-(5- mp: 141-142° C. NMR: δ 1.57(s, 6H), 2.48(s,Methyl- 3H), 3.11(s, 3H), 6.70(d, J=2.7Hz, 1H), 6.91(d, thienyl)J=3.6Hz, 1H), 7.81(s, 4H). IR(cm⁻¹): 2926, 1702, 1317, 1141, 770. 1232-(5- NMR: δ 1.58(s, 6H), 2.31(s, 3H), 3.11(s, 3H), Fomyl- 7.08(d,J=3.6Hz, 1H), 7.26(d, J=3.6Hz 2H), furanyl) 7.08(s, 4H). IR(cm⁻¹): 1733,1709, 1696, 1407, 1317, 1169. 124 2-(5-Bromo- NMR: δ 1.57(s, 6H),3.11(s, 3H), 6.88(d, thienyl) J=3.6Hz, 1H, 7.00(d, J=3.6Hz, 1H), 7.97(m,4H).

Compounds of Example 125˜Example 159 were prepared by procedures similarto the synthetic procedure in Step 4of Example 22.

EXAMPLE 125˜EXAMPLE 159

Example R Melting point & spectral data 125 3-F, mp: 204-205° C. NMR: δ1.57(s, 6H), 4.96 (br s, 5-F 2H), 6.78(m, lH), 6.82(m, 2H), 7.78(d,J=8.7Hz, 2H), 7.96(d, J=8.7Hz, 2H). IR(cm⁻¹): 3267, 1686, 1218, 1160.126 3-Cl mp: 194-195° C. NMR: δ l.57(s, 6H), 4.89(br s, 2H), 7.14(m,lH), 7.31(m, 3H), 7.78(d, J=9.0Hz, 2H), 7.93(d, J=8.4Hz, 2H). IR(cm⁻¹):3249, 1689, 1614, 1344, 1161. 127 3-Cl, mp: 208-209° C. NMR: δ 1.57(s,6H), 4.91(br s, 4-Cl 2H), 7.09(dd, J=8.4, 1.8Hz, 1H), 7.43(d, J=5.1Hz,1H), 7.45(s, 1H), 7.78(d, J=8.4Hz, 2H), 7.95(d, J=8.7Hz, 2H). IR(cm⁻¹):3339, 3265, 1687, 1616, 1342, 1162. 128 3-CH₃ Mp: 188-189° C. NMR: δ1.57(s, 6H), 2.35(s, 3H), 4.82(br s, 2H), 7.01(m, 1H), 7.15(m, 2H),7.25(m, 1H), 7.79(d, J=8.7Hz, 2H), 7.89(d, J=8.7Hz, 2H). IR(cm⁻¹): 3363,3266, 1686, 1345, 1159. 129 3-F mp: 155-156° C. NMR: δ 1.58(s, 6H),4.90(br s, 2H), 7.04(m, 3H), 7.30(m, 1H), 7.78(d, J=8.4Hz, 2H), 7.93(d,J=8.4Hz, 2H). IR(cm⁻¹): 3339, 3255, 1692, 1620, 1343, 1261, 1161.MS(FAB): 362(m + 1). 130 2-F, mp: 175-176° C. NMR: δ 1.59(s, 6H),4.95(br s, 4-F 2H), 6.86(m, 1H), 6.98(m, 1H), 7.32(m, 1H), 7.76 (d,J=9.0Hz 2H), 7.94(d, J=8.4Hz, 2H). IR(cm⁻¹): 3354, 3258, 1692, 1698,1501, 1342, 1268, 1160, 1098. 131 3-Me, mp: 175° C. NMR: δ 1.56(s, 6H),2.24(s, 3H), 2.28 4-Me (s, 3H), 5.09(br s, 2H), 6.94(d, J=7.8Hz, 1H),7.07(d, J=7.5Hz, 1H), 7.79(d, J=8.4Hz, 2H), 7.86(d, J=8.7Hz, 2H).IR(cm⁻¹): 3349, 3258, 1689, 1620, 1550, 1345, 1160, 728. 132 2- mp: 177°C. NMR: δ 1.56(s, 6H), 3.52(s, 3H), OMe, 3.85(s, 3H), 4.87(br s, 2H),6.49(s, 1H), 6.58(dd, 4-OMe J=2.4, 2.4Hz, 1H), 7.14(d, J=8.4Hz, 1H),7.78(d, J=8.7Hz, 2H), 7.88(d, J=8.7Hz, 2H). IR(cm⁻¹): 3346, 3253, 1688,1592, 1161, 897, 759. MS(FAB): 380(m + 1). 133 H mp: 180-182° C. NMR: δ1.58(s, 6H), 4.91(br s, 2H), 7.30(m, 5H), 7.78(d, J=8.7Hz, 2H), 7.89(d,J=8.4Hz, 2H). IR(cm⁻¹): 3375, 3245, 1697, 1617, 1559, 1395, 1241, 1161,899, 752. 134 3-Cl, mp: 178° C. NMR: δ l.57(s, 6H), 4.88(br s, 2H), 4-F7.14(m, 2H), 7.39(m, 1H), 7.78(d, J=9.0Hz, 2H), 7.94(d, J=8.7Hz, 2H).IR(cm⁻¹): 3321, 3135, 1657, 1543, 1256, 1162, 912, 802. 135 3-OMe mp:259-260° C. NMR: δ 1.57(s, 6H), 3.78(s, 3H), 4.90(br s, 2H), 6.86(m,4H), 7.79(m, 2H), 7.89(m, 2H). IR(cm⁻¹): 3385, 3245, 1695, 1547, 1321,1164, 900, 679. 136 4- mp: 219-220° C. NMR: δ 1.55(s, 6H), 2.62(s, 3H),Acetyl 5.00(br s, 2H), 7.26(d, J=8.7Hz, 2H), 7.75(d, J=8.7Hz, 2H),7.78(d, J=8.7Hz, 2H), 7.95(d, J=8.7Hz, 2H). IR(cm⁻¹): 3367, 3261, 1684,1164, 913. MS(FAB): 386(m + 1). 137 2-Me mp: 185-186° C. NMR: δ 1.58(s,6H), 2.11(s, 3H), 4.99(br s, 2H), 7.21(m, 1H), 7.29(m, 1H), 7.30(m, 2H),7.67(m, 2H), 7.83(m, 2H). IR(cm⁻¹): 3323, 1682, 1346, 1163, 912. 1383-F, mp: 210-211° C. NMR: δ 1.58(s, 6H), 5.06(br s, 4-F 2H), 6.81(m,1H), 7.18(m, 2H), 7.78(d, J=8.4Hz, 2H), 7.95(d, J=8.4Hz, 2H). IR(cm⁻¹):3267, 1691, 1608, 1335, 1219, 1160. MS(FAB): 380(m + 1). 139 4-CH₃ mp:163-164° C. NMR: δ 1.57(s, 6H), 2.37(s, 3H), 4.85(br, 2H), 7.18(m, 4H),7.79(d, J=8.9Hz, 2H), 7.90(d, J=9.0Hz, 2H). IR(cm⁻¹): 3237, 1682, 1390,1341, 1161. MS(FAB): 358(m + 1). 140 4-Cl mp: 230-231° C. NMR: δ 1.57(s,6H), 4.94(br s, 2H), 7.23(d, J=8.7Hz, 2H), 7.36(d, J=8.4Hz, 2H), 7.78(d,J=8.4Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 3333, 1685, 1387, 1342,1219, 1161. 141 4-SMe mp: 96-97° C. NMR: δ 1.57(s, 6H), 2.50(s, 3H),4.91(br s, 2H), 7.23(m, 4H), 7.81(m, 2H), 7.91(m, 2H). IR(cm⁻¹): 3374,3228, 1683, 1339, 1161, 1094, 902, 805. MS(FAB): 390(m + 1). 142 3-F,mp: 205° C. NMR: δ 1.59(s, 6H), 5.20(br s, 2H), 4-Ph 7.16(m, 2H),7.46(m, 5H), 7.86(d, J=8.7Hz, 2H), 7.97(d, J=8.7Hz, 2H). IR(cm⁻¹): 3324,3251, 1692, 1611, 1402, 1338, 1161, 854, 728. 143 3-Br mp: 101-102° C.NMR: δ 1.58(s, 6H), 4.87(br s, 2H), 7.57(m, 4H), 7.84(d, J=8.4Hz, 2H),7.94(d, J=8.4Hz, 2H). IR(cm⁻¹): 3332, 3241, 1693, 1615, 1404, 1161, 912,726. 144 5-iso- mp: 213° C. NMR: δ 1.23(d, J=6.9Hz, 6H), 1.57(s, Pr,6H), 2.87(m, 1H), 3.52(s, 3H), 4.85(br s, 2H), 6.84 2-OMe (d, J=6.9Hz,lH), 7.07(s, 1H), 7.22(d, J=2.1Hz, 1H), 7.76(d, J=8.7Hz, 2H), 7.87(d,J=8.7Hz, 2H). IR (cm⁻¹): 3328, 3257, 1640, 1530, 1200, 1163, 1029, 746.145 3-iso- mp: 133° C. NMR: δ 1.21(d, J=6.9Hz, 6H), 1.57(s, Pr 6H),2.87(m, 1H), 4.91(br s, 2H), 7.22(m, 4H), 7.80 (d, J=8.7Hz, 2H), 7.90(d,J=8.7Hz, 2H). IR(cm⁻¹): 3370, 3258, 1611, 1247, ll6l, 9l8, 801, 605.MS(FAB): 386 (m + 1). 146 4-SEt mp: 185° C. NMR: δ 1.35(t, J=7.5Hz, 3H),1.57(s, 6H), 2.97(m, 2H), 5.01(br s, 2H), 7.22(m, 4H), 7.80 (d, J=8.7Hz,2H), 7.91(d, J=8.7Hz, 2H). IR(cm⁻¹): 3354, 3257, 2927, 1695, 1682, 1587,1343, 1161, 902. 147 2-OMe mp: 137° C. NMR: δ 1.57(s, 6H), 3.54(s, 3H),5.08 (br s, 2H), 6.92(d, J=8.4Hz, 1H), 7.02(t, J=8.7Hz, 1H), 7.22(d,J=8.7Hz, 1H), 7.35(t, J=7.5Hz, 1H), 7.74(d, J=8.7Hz, 2H), 7.86(d,J=8.7Hz, 2H). IR(cm⁻¹): 3335, 3252, 2929, 1685, 1588, 1404, 1161, 902,845. 148 4-n-Bu mp: 107-108° C. NMR: δ 0.94(t, J=7.5Hz, 3H), 1.37(m,2H), 1.56(s, 6H), 1.63(m, 2H), 2.62(t, J=7.5Hz, 2H), 4.94(br s, 2H),7.18(s, 4H), 7.80(d, J=8.4Hz, 2H), 7.89(d, J=8.4Hz, 2H). IR(cm⁻¹): 3341,3241, 2929, 1682, 1593, 1342, 1160. 149 3-Cl, mp: 209-210° C. NMR: δ1.57(s, 6H), 4.90(br s, 5-Cl 2H), 7.19(d, J=1.8Hz, 2H), 7.34(t, J=1.8Hz,1H), 7.78(d, J=8.7 Hz, 2H), 7.96(d, J=9.0Hz, 2H). IR (cm⁻¹): 3352, 3266,1698, 1558, 1457, 1165, 899, 807. 150 3,4,5- mp: 171-172° C. NMR: δ1.57(s, 6H), 3.77(s, 6H), tri- 3.87(s, 3H), 4.88(br s, 2H), 6.48(s, 2H),7.84(d, OMe J=9.0Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 3341, 1686,1586, 1344, 116l. 151 4-OH mp: 164-165° C. NMR: δ l.51(s, 6H), 5.13(brs, 2H), 6.06(s, lH), 6.85(m, 2H), 7.08(m, 2H), 7.96(m, 2H), 8.04(m, 2H).IR(cm⁻¹): 3352, 3266, 1698, 1558, 1457, 1165, 899, 807. 152 4-F, mp:168-170° C. NMR: δ 1.56(s, 6H), 3.92(s, 3H), 3-OMe 4.90(br s, 2H),6.96(m, 3H), 7.79(m, 2H), 7.93(m, 2H). IR(cm⁻¹): 3352, 3245, 1697, 1519,1271, 1024, 912, 729. 153 4- mp: 180-181° C. NMR: δ l.55(s, 6H), 2.26(s,6H), OMe, 3.74(s, 3H), 4.91(br s, 2H), 6.81(m, 1H), 7.53(m, 3-Me, 1H),7.83(m, 2H), 7.91(m, 2H). IR(cm⁻¹): 3325, 5-Me 1701, 1458, 1287, 1127.MS(FAB): 372 (m + 1) 154 4-Et mp: 133-135° C. NMR: δ 1.25(t, J=7.8Hz,3H), l.56(s, 6H), 2.67(q, J=7.8Hz, 3H), 4.92(br s, 2H), 7.20(m, 4H),7.79(m, 2H), 7.88(m, 2H). IR(cm⁻¹): 3362, 3259, 2930, 1697, 1594, 1389,1343, 1161. 155 2-F mp: 188-189° C. NMR: δ 1.58(s, 6H), 5.07(br s, 2H),7.08(m, 1H),7.21(dt, J=75, 0.9Hz, 1H), 7.35 (m, 2H), 7.75(d, J=8.7Hz,2H), 8.01(d, J=8.7Hz, 2H). IR(cm⁻¹): 3365, 3257, 1685, 1525, 1339, 1165,795, 679. 156 3-NH₂ mp: 217-218° C. NMR: δ 1.59(s, 6H), 5.00(br s, 2H),6.90(m, 1H), 7.05(m, 3H), 7.76(m, 2H), 7.93 (m, 2H). IR(cm⁻¹): 3311,3222, 1695, 1489, 1422, 1344, 1161. 157 2-F, mp: 182-183° C. NMR: δ1.56(s, 6H), 5.14(br s, 5-F 2H), 7.43(m, 2H), 7.70(m, 1H), 7.81(m, 2H),7.87 (m, 2H). IR(cm⁻¹): 3362, 3259, 2965, 1697, 1559, 1387, 1162. 1583-NO₂ mp: 233-234° C. NMR: δ l.61(s, 6H), 5.09(br s, 2H), 7.56(m, 1H),7.63(m, 1H), 7.76(d, J=8.7Hz, 2H), 7.95(d, J=8.7Hz, 2H), 8.17(m, 2H).IR(cm⁻¹): 3365, 3255, 1690, 1594, l529, 1348, 1161. 159 5-F, mp:186-187° C. NMR: δ 1.58(s, 6H), 2.35(s, 3H), 2-Me 5.04(br s, 2H),6.97(m, 1H), 7.13(m, 2H), 7.77(d, J=8.7Hz, 2H), 7.90(d, J=8.7Hz, 2H).IR(cm⁻¹): 3386, 3237, 169l, 1406, 1219, 1160.

Compounds of Example 160˜Example 165 were prepared by procedures similarto the synthetic procedure of Example 28.

EXAMPLE 160˜EXAMPLE 165

Example AR Melting point & spectral data 160 2-Furanyl mp: 156-157° C.NMR: δ 1.56(s, 6H), 4.90(br s, 2H), 6.51(m, 1H), 6.87(m, 1H), 7.37(m,1H), 7.93(m, 2H), 8.01(d, J=9.0Hz, 2H). IR (cm⁻¹): 3365, 3257, 1685,1525, 1339, 1165, 795, 729. 161 3-Thienyl mp: 155-156° C. NMR: δ 1.56(s,6H), 4.94(br s, 2H), 6.93(m, 1H), 7.32(m, 1H), 7.51(m, 1H), 7.86(m, 2H),7.96(m, 2H). IR(cm⁻¹): 3353, 3254, 3105, 1695, 1616, 1343, 1158, 912,729. 162 2-Naphthyl mp: 178-180° C. NMR: δ 1.62(s, 6H), 4.85(br s, 2H),7.26(m, 2H), 7.50(m, 2H), 7.83(m, 3H), 7.85(m, 4H). IR(cm⁻¹): 3345,3252, 1674, 1558, 1160, 801, 743, 679. MS(FAB): 393(m + 1) 1631-Naphthyl mp: 200-201° C. NMR: δ 1.66(s, 3H), 1.70(s, 3H), 4.76(br s,2H), 7.38(m, 2H), 7.52(m, 3H), 7.62(m, 2H), 7.74(m, 2H), 7.92(m, 2H). IR(cm⁻¹): 3363, 3278, 1683, 1615, 1558, 1339, 1190, 1095, 912, 739. 1644-(1-N- NMR: δ 1.53(s, 6H), 3.92(s, 3H), 5.12(br s, Methyl- 2H), 7.36(s,1H), 7.73(s, 1H), 7.98(s, 4H). pyrazolyl) 165 3-Pyridyl mp: 205-206° C.NMR: δ 1.60(s, 6H), 4.89 (br s, 2H), 7.36(m, 1H), 7.72(m, 1H), 7.77(d,J=8.7Hz, 2H), 7.94(d, J=8.7Hz, 2H), 8.46(d, J=1.2Hz, 1H), 8.57(dd,J=3.3, 1.5Hz, 1H).

EXAMPLE 166

2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanoneStep 1: Preparation of2-(3-fluorophenyl)-1-{4-(methylthio)phenyl}-ethanone

To a stirred solution of 68 ml thioanisole in 600 ml dichloromethane at0° C., were added slowly in a series aluminum chloride (77.3 g) and(3-fluorophenyl)acetyl chloride (100 g). The reaction mixture wasstirred for an hour, after which 1 L of aqueous HCl was added slowly tothe reaction mixture. The quenched mixture was stirred for another hour,which was followed by extraction with methylene chloride. The organiclayer was washed with brine and then was dried over anhydrous magnesiumsulfate. The magnesium sulfate was filtered off and the filtrate wasconcentrated in vacuo. The resulting residue was purified byrecrystallization from hexane/dichloromethane to yield 142.9 g of2-(3-fluorophenyl)-1-{4-(methylthio)-phenyl}-ethanone. mp: 94.5-95.5° C.NMR: δ2.52 (s, 3H), 4.23 (s, 2H), 6.95-7.05 (m, 3H),7.25-7.30 (m, 3H),7.92 (d, J=8.7 Hz, 2H).

Step 2: Preparation of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone

To a stirred solution of2-(3-fluorophenyl)-1-{4-(methylthio)phenyl}-ethan-1-one (100 g) in 1 Ldry THF, was added portion-wise 26 g of 95 % sodium hydride at 0° C. Thereaction solution was stirred at the same temperature for 1 hour. Then69 g of α-bromo-isobutyryl cyanide diluted in 25 ml dry THF was addeddropwise to the stirred solution at 0° C. The reaction mixture wasstirred overnight while allowing to warm gradually to room temperature.The solution was concentrated in vacuo, to which was added 50 ml water.The aqueous solution was extracted with ethylacetate (1 L). The organiclayer was concentrated in vacuo and purified by column chromatography(hexane/ethylacetate=6:1) to give 102 g of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone.mp: 106° C. NMR: δ1.55 (s, 6H), 2.50 (s. 3H), 6.97-7.11 (m, 3H), 7.18(d, J=9.0 Hz, 2H), 7.26-7.36 (m, 1H), 7.55 (d, J=9.0 Hz, 2H).

Compounds of Example 167˜Example 173 were prepared by followingprocedures similar to the procedure used for the synthesis of Example166.

EXAMPLE 167˜EXAMPLE 173

Example R Melting point & spectral data 167 H mp: 109-110° C. NMR: δ1.55(s, 6H), 2.49(s, 3H), 7.16(d, J=8.7Hz, 2H), 7.27-7.55(m, 5H),7.56(d, J=8.7Hz, 2H). IR(cm⁻¹): 2979, 1693, 1612, 1388, 1237, 1170,1094, 829, 750. 168 3-Cl Oil. NMR: δ 1.55(s, 6H), 2.49(s, 3H), 7.15-7.22(m, 3H), 7.27-7.31(m, 2H), 7.33-7.36(m, 1H), 7.54 (d, J=8.7Hz, 2H). 1693-CF₃ NMR: δ 1.56(s, 6H), 2.49(s, 3H), 7.18(d, J=9.0Hz, 2H),7.51-7.62(m, 6H). 170 4-NO₂ NMR: δ 1.57(s, 6H), 2.51(s, 3H), 7.21(d,J=8.7Hz, 2H), 7.53(d, J=8.7Hz, 2H), 7.54(d, J=9.0Hz, 2H), 8.21(d,J=8.7Hz, 2H). 171 4-OMe mp: 119-117° C. NMR: δ 1.54(s, 6H), 2.49(s, 3H),3.83(s, 3H), 6.91(d, J=9.0Hz, 2H), 7.16(d, J=8.7Hz, 2H), 7.23(d,J=9.0Hz, 2H), 7.53(d, J=8.7Hz, 2H). 172 2-F, mp: 90.5-91° C. NMR: δ1.56(s, 6H), 2.49(s, 3H), 5-F 7.01-7.06(m, 3H), 7.17(d, J=8.7Hz, 2H),7.53(d, J=8.4Hz, 2H). 173 3-F, mp: 122-123° C. NMR: δ 1.55(s, 6H),2.51(s, 3H), 5-F 6.71-6.78(m, 1H), 6.84-6.92(m, 2H), 7.21(d, J=8.7Hz,2H), 7.55(d, J=9.0Hz, 2H).

EXAMPLE 174

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(2-thienyl)-3(2H)-furanone

2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(2-thienyl)-3(2H)-furanone wasprepared according to a procedure similar to the synthetic procedure inExample 166. mp: 113˜114° C. NMR; δ1.55 (s, 6H), 2.51 (s, 3H), 7.05 (dd,J=5.1, 3.9 Hz, 1H), 7.11 (dd, J=3.6, 1.2 Hz, 1H), 7.22 (d, J=8.4 Hz,2H), 7.33 (d, J=5.1 Hz, 1H), 7.68 (d, J=9.0 Hz, 2H).

EXAMPLE 175

2,2-Dimethyl-4-(fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanoneStep 1: Preparation of4-bromo-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a solution of2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone (135 mg) in 25ml of CCl₄, were added 1 ml acetic acid and 0.1 ml bromine. The reactionmixture was stirred at room temperature for 2.5 hr. Then the reactionwas quenched by adding 10 ml of saturated aqueous sodium thiosulfate.The volatile materials were removed in vacuo, which was followed byextraction with dichloromethane (50 ml×3). The organic layer was driedover anhydrous magnesium sulfate and the magnesium sulfate was filteredoff. The filtrate was concentrated in vacuo and the crude product waspurified by column chromatography (hexane/ethylacetate=1:1) to give 68mg of 4-bromo-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone.mp: 117-118° C. NMR: δ1.55 (s, 6H), 2.79 (s, 3H), 7.81 (d, J=8.2 Hz,2H), 8.38 (d, J=8.2 Hz, 2H). IR (cm⁻¹): 1706, 1601,1555, 1191, 1052.

Step 2: Preparation of2,2-dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To 53 mg of4-bromo-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone in 30ml of benzene, were added 25 mg of Pd(Ph₃)₄, 25.4 mg of(4-fluorobenzene)boronic acid and 0.22 ml of 2 M aqueous sodiumcarbonate. The reaction mixture was stirred at 80˜90° C. for 12 hours.Then the reaction mixture was concentrated under reduced pressure. Theresulting residue was extracted with CH₂Cl₂ and brine and the organiclayer was dried over anhydrous MgSO₄. The organic layer was evaporatedoff in vacuo and the crude product was purified by column chromatography(hexane/ethylacetate) to yield 15 mg of2,2-dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone.mp: 134-136° C. NMR: δ1.57 (s, 6H), 2.75 (s, 3H), 7.08 (m, 2H) 7.27 (m,2H), 7.65 (d, J=8.2 Hz, 2H), 7.80 (d, J=8.2 Hz, 2H). IR (cm⁻¹): 2925,2854, 1695, 1618, 1590, 1237, 1051, 758.

EXAMPLE 176

2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a stirred solution of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone(2.0 g, Example 166) in 50 ml dichloromethane, was added 1.5 g ofm-chloroperoxybenzoic acid at 0° C. The reaction solution was stirred atthe same temperature for one and half hours, after which 30 ml 5%aqueous sodium bicarbonate was added and the solution was stirred foranother 10 minutes. Then the reaction mixture was concentrated in vacuo,and the resulting residue was extracted with 50 ml water anddichloromethane (30 ml×3). The organic layer was concentrated in vacuoand was purified by column chromatography (hexane/ethylacetate=1:1) togive 1.3 g of2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone.mp: 143-144° C. NMR: δ1.58 (s, 6H), 2.76(s, 3H), 7.26-7.08 (m, 3H),7.30-7.38 (m, 1H), 7.65 (d, J=8.2 Hz, 2H), 7.80 (d, J=8.2 Hz, 2H).

EXAMPLE 177

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanonewas prepared by following a procedure similar to the synthetic procedurein Example 176. mp: 133-134° C. NMR: δ1.57 (s, 6H), 2.77 (s, 3H),6.75-6.87 (m, 3H), 7.69 (d, J=8.2 Hz, 2H), 7.80 (d, J=8.2 Hz, 2H).

EXAMPLE 178

4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4(methylsulfonyl)phenyl}-3(2H)-furan-3-thione

90 mg of4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone(Example 2) in 30 ml toluene was stirred at reflux for 12 hours in thepresence of 60 mg of Lawesson's reagent, Then the solvent was removed invacuo and the resulting residue was extracted with 50 ml water andethylacetate (50 ml×3). The organic layer was concentrated under reducedpressure and was purified by column chromatography(hexane/ethylacetate=4:1) to give 30 mg of4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H1)-furan-3-thioneas a solid. mp: 165-166° C. NMR: δ1.71 (s, 6H), 3.07 (s, 3H), 7.12 (m,1H), 7.21 (d, 1H), 7.36 (dd, 1H), 7.81 (d, J=8.4 Hz, 2H), 7.95 (d, J=8.4Hz, 2H). IR (cm⁻¹): 1580, 1553, 1502, 1319, 1261, 1154, 957, 760.

Compounds of Example 179˜Example 181 were prepared according toprocedures similar to the synthetic procedure in Example 178.

EXAMPLE 179˜EXAMPLE 181

Example R Melting point & spectral data 179 4-F NMR: δ 1.69(s, 6H),3.12(s, 3H), 7.23(m, 2H), 7.48 (m, 1H), 7.36(dd, J=8.4, 2.4Hz, 1H),8.11(d, J=8.1Hz, 2H), 8.48(d, J=8.4Hz, 2H). 180 3-F mp: 106-107° C. NMR:δ 1.70(s, 6H), 3.07(s, 3H), 7.01(m, 2H), 7.12(m, 1H), 7.40(m, 1H),7.79(d, J=8.1Hz, 2H), 7.92(d, J=8.1Hz, 2H). IR(cm⁻¹); 1616, 1584, 1397,1319, 1255, 1154, 957. 181 3-F, mp: 126-127° C. NMR: δ 1.72(s, 6H),3.08(s, 3H), 5-F 6.84(m, 3H), 7.80(d, J=8.7Hz, 2H), 7.95(d, J=8.7Hz,2H). IR(cm⁻¹): 1624, 1593, 1391, 1323, 1284, 1120, 988.

EXAMPLE 182

5-[{4-{(Acetylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone

360 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone(Example 129) in 30 ml in dichloromethane was reacted with 0.8 ml aceticanhydride in the presence of 0.5 ml triethylamine and 50 mg of4-(N,N-dimethylamino)pyridine at room temperature for 12 hours. Thereaction mixture was concentrated in vacuo, which was followed byextraction with 30 ml water and dichloromethane (30 ml×3). The organiclayer was concentrated under reduced pressure and then was purified bycolumn chromatography (hexane/ethylacetate 2:1) to afford 397 mg of5-[4-{(acetylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluoro-phenyl)-3(2H)-furanoneas a solid. mp: 178-179° C. NMR: δ1.57 (s, 6H), 2.08 (s, 3H), 7.05 (m,3H), 7.34 (m, 1H), 7.82 (d, J=8.4 Hz, 2H), 8.05 (d, J=8.4 Hz, 2H), 8.20(br s, 1H). IR (cm⁻¹): 3238, 3198, 1431, 1261, 1159.

EXAMPLE 183

5-[4-{(n-Butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone

360 mg of5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone(Example 129) in 30 ml dichloromethane was reacted with 0.8 ml butyricanhydride in the presence of 0.5 ml triethylamine and 50 mg of4-(N,N-dimethylamino)pyridine at room temperature for 12 hours. Thereaction mixture was concentrated in vacuo, which was followed byextraction with 30 ml water and dichloromethane (30 ml×3). The organiclayer was concentrated under reduced pressure and then was purified bycolumn chromatography hexane/ethylacetate 2:1) to afford 363 mg of5-[4-{(n-butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanoneas a solid. mp: 188-189° C. NMR: δ0.89 (t, J=7.5 Hz, 3H), 1.58 (s, 6H),1.60 (m, 2H), 2.24 (t, J=7.5 Hz, 2H), 7.05 (m, 3H), 7.34 (m, 1H), 7.82(d, J=8.4 Hz, 2H), 8.06 (d, J=8.4 Hz, 2H), 8.19 (br s, 1H). IR (cm⁻¹):3195, 3140, 1698, 1435, 1350, 1190.

EXAMPLE 184

2,2-Dimethyl-5-{4-(N-methylaminosulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone

500 mg of2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone(Example 166) was stirred in 15 ml trifluroacetic anhydride for an hourat 0° C. and then the solvent was removed in vacuo. The resultingresidue was dissolved in 10 ml 1:1 methanol/triethylamine and wasstirred at 0° C. for an hour. The solution was concentrated underreduced pressure. Then the resulting residue was stirred in 15 mldichloromethane, to which was added 5 ml acetic acid saturated withchlorine. After the solution was stirred for 30 minutes at 0° C., thesolvent and the unreacted chlorine was removed in vacuo. The resultingresidue was dissolved in 5 ml toluene and the toluene was evaporated offin vacuo. The resulting residue was dissolved in 20 ml THF and reactedwith 1 ml of 40% aqueous methylamine for 2 hours at 0° C. The reactionsolution was concentrated in vacuo, which was followed by extractionwith 30 ml water and dichloromethane (30 ml×3). The organic layer waswashed with brine and concentrated under reduce pressure. The resultingresidue was purified by column chromatography (hexane/ethylacetate=3:2)to give 155 mg of2,2-dimethyl-5-{4-(N-methylaminosulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanoneas a solid. mp: 176-177° C. NMR: δ1.58 (s, 6H), 2.70 (d, J=5.1 Hz, 3H),4.35 (q, J=5.4 Hz, 1H), 7.04 (m, 3H), 7.33 (m, 1H), 7.89 (d, J=8.7 Hz,2H), 7.86 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3285, 1696, 1402, 1388, 1261,1160.

EXAMPLE 185

2,2-Dimethyl-5-{4-(N-ethylaminosulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone

By following the procedure in Example 184 except using 70% aqueousethylamine, the titled compound was obtained. mp: 113-114° C. NMR: δ1.13(t, J=7.2 Hz, 3H), 1.57 (s, 6H), 3.06 (m, 2H), 4.34 (t, J 6.0 Hz, 1H),7.03 (m, 3H), 7.32 (m, 1H), 7.78 (d, J=8.7 Hz, 2H), 7.86 (d, J=9.0 Hz,2H). IR (cm⁻¹): 3271, 1694, 1619, 1592, 1387, 1260, 1159.

Compounds of Example 186˜Example 218 were prepared by a proceduresimilar to the synthetic procedure in Step 6 of Example 31.

EXAMPLE 186˜EXAMPLE 218

Example R Melting point & spectral data 186 4-F mp: 111-114° C. NMR: δ0.95(t, J=7.2Hz, 3H), 1.54(s, 3H), 1.97(m, 2H), 3.08(s, 3H), 7.09(m,2H), 7.24(m, 2H), 7.84(d, J=8.1Hz, 2H), 7.95(d, J=8.7Hz, 2H). IR(cm⁻¹):2972, 1696, 1591, 1511, 1318, 1149, 913, 745, 551 187 3-F mp: 107-108°C. NMR: δ 0.95(t, J=7.2Hz, 3H), 1.55(s, 3H), 1.97(m, 2H), 3.08(s, 3H),7.04(m, 2H), 7.35(m, 2H), 7.84(d, J=8.7Hz, 2H), 7.96(d, J=8.4Hz, 2H).IR(cm⁻¹): 2926, 1698, 1403, 1319, 1149, 961, 850, 769, 552 188 2-F mp:108-109° C. NMR: δ 0.96(t, J=7.2Hz, 3H), 1.56(s, 3H), 1.99(m, 2H),3.06(s, 3H), 7.10(m, 1H), 7.28(m, 3H), 7.83(d, J=8.4Hz, 2H), 7.94(d,J=8.7Hz, 2H). IR(cm⁻¹): 2975, 2929, 1699, 1595, 1404, 1319, 1150, 969,766, 552. 189 3-F, mp: 106-108° C. NMR: δ 0.94(t, J=7.5Hz, 3H), 4-F1.54(s, 3H), 1.97(m, 2H), 3.09(s, 3H), 7.00(m, 1H), 7.16(m, 2H), 7.83(d,J=8.4Hz, 2H), 7.973(d, J=8.4Hz, 2H). IR(cm⁻¹): 2931, 1698, 1597, 1518,1277, 1160, 959, 868, 770, 552. 190 3-Cl, mp: 145-146° C. NMR: δ 0.95(t,J=7.5Hz, 3H), 4-F 1.54(s, 3H), 1.97(m, 2H), 3.09(s, 3H), 7.13(m, 2H),7.37(m, 1H), 7.84(d, J=8.7Hz, 2H), 7.97(d, J=8.7Hz, 2H). IR(cm⁻¹): 2974,1696, 1622, 1502, 1319, 1252, 1150, 956, 766, 726, 552. 191 4-OMe mp:130-133° C. NMR: δ 0.94(t, J=7.5Hz, 3H), 1.55(s, 3H), 1.97(m, 2H),3.07(s, 3H), 3.83(s, 3H), 6.93(d, J=9.0Hz, 2H), 7.19(d, J=8.7Hz, 2H),7.90(m, 4H). IR(cm⁻¹): 2929, 1694, 1593, 1613, 1317, 1148, 913, 744,552. 192 4-Me mp: 48-49° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H),1.96(m, 2H), 2.38(s, 3H), 3.07(s, 3H), 7.17(m, 4H), 7.89(m, 4H).IR(cm⁻¹): 2974, 2927, 1696, 1624, 1514, 1402, 1318, 1149, 958, 769, 552.193 3-Me mp: 48-49° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H), 1.97(m,2H), 2.35(s, 3H), 3.07(s, 3H), 7.00(m, 1H), 7.14(m, 2H), 7.26(m, 1H),7.85(d, J=8.7Hz, 2H), 7.92(d, J=8.4Hz, 2H). IR(cm⁻¹): 2974, 2928, 1696,1621, 1403, 1319, 1149, 957, 768, 552. 194 3-CF₃ mp: 45-46° C. NMR: δ0.97(t, J=7.2Hz, 3H), 1.56(s, 3H), 1.99(m, 2H), 3.08(s, 3H), 7.53(m,4H), 7.83(d, J=8.1Hz, 2H), 7.96(d, J=8.1Hz, 2H). IR (cm⁻¹): 2977, 2932,1696, 1625, 1594, 1404, 1326, 1232, 1151, 1091, 958, 912, 769, 701, 552.195 3-Cl mp: 94-95° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H), 1.98(m,2H), 3.08(s, 3H), 7.13(m, 1H), 7.30(m, 3H), 7.84(d, J=8.7Hz, 2H),7.96(d, J=8.7Hz, 2H). IR(cm⁻¹): 2975, 2930, 1699, 1620, 1403, 1319,1150, 958, 742, 552. 196 3- mp: 135-136° C. NMR: δ 0.97(t, J=7.2Hz, 3H),Acetyl 1.54(s, 3H), 1.98(m, 2H), 2.58(s, 3H), 3.07(s, 3H), 7.48(m, 3H),7.82(d, J=8.7Hz, 2H), 7.88(m, 1H), 7.94(d, J=9.0Hz, 2H). IR(cm⁻¹): 2927,1694, 1590, 1318, 1149, 959, 801, 771, 552. 197 3,4- mp: 160-163° C.NMR: δ 0.94(t, J=7.5Hz, 3H), meth- 1.53(s, 3H), 1.96(m, 2H), 3.08(s,3H), 6.00(s, 2H), ylene- 6.73(m, 2H), 6.84(m, 1H), 7.88(d, J=8.4Hz, 2H),dioxy 7.95(d, J=8.4Hz, 2H). IR(cm⁻¹): 2922, 2851, 1696, 1596, 1507,1438, 1404, 1318, 1243, 1149, 1035, 958, 769, 552. 198 4-Cl, mp:168-170° C. NMR: δ 0.96(t, J=7.2Hz, 3H), 3-CF₃ 1.56(s, 3H), 1.98(m, 2H),3.09(s, 3H), 7.37(m, 1H), 7.51(m, 1H), 7.64(m, 1H), 7.82(d, J=8.7Hz,2H), 7.99(d, J=8.4Hz, 2H). IR(cm⁻¹):2929, 1697, 1624, 1592, 1317, 1149,913, 744, 552. 199 4-Et mp: 45° C. NMR: δ 0.95(t, J=6.9Hz, 3H), 1.26(t,J=7.8Hz, 3H), 1.53(s, 3H), 1.96(q, J=6.9Hz, 2H), 2.67(q, J=7.8Hz, 2H),3.07(s, 3H), 7.15-2.26(m, 4H), 7.85-7.94(m, 4H). IR(cm⁻¹): 1693, 1594,1319, 1149, 913, 745, 552. 200 3-OMe NMR: δ 0.95(t, J=7.5Hz, 3H),1.54(s, 3H), 1.98(m, 2H), 3.07(s, 3H), 3.78(s, 3H), 6.85(m, 3H), 7.28(m,1H), 7.86(d, J=8.7Hz, 2H), 7.93(d, J=8.4Hz, 2H). IR(cm⁻¹): 2931, 2838,1696, 1621, 1403, 1318, 1149, 1036, 957, 769, 552. 201 3-iso- NMR: δ0.96(t, J=7.5Hz, 3H), 1.19(s, 3H), 1.21(s, Pr 3H), 1.54(s, 3H), 1.97(m,2H), 2.87(m, 1H), 3.06(s, 3H), 7.09(m, 2H), 7.26(m, 2H), 7.89(m, 4H). IR(cm⁻¹): 2964, 2928, 1696, 1620, 1402, 1319, 1149, 958, 771, 552. 2024-n-Pr NMR: δ 0.96(m, 6H), 1.53(s, 3H), 1.66(m, 2H), 1.95(m, 2H),2.61(t, J=7.5Hz, 2H), 3.07(s, 3H), 7.18(m, 4H), 7.89(m, 4H). IR(cm⁻¹):2966, 2930, 1697, 1510, 1401, 1319, 1149, 958, 769, 552. 203 4-n-Bu NMR:δ 0.94(m, 6H), 1.38(m, 2H), 1.53(s, 3H), 1.62(m, 2H) 1.96(m, 2H),2.63(t, J=7.8Hz, 2H), 3.07(s, 3H), 7.18(m, 4H), 7.86(d, J=8.4Hz, 2H),7.93(d, J=8.4Hz, 2H). IR(cm⁻¹): 2969, 2929, 1697, 1622, 1594, 1401,1319, 1149, 958, 769, 552. 204 3-Me, mp: 124-126° C. NMR: δ 0.95(t,J=7.5Hz, 3H), 4-Me 1.53(s, 3H), 1.96(m, 2H), 2.25(s, 3H), 2.28(s, 3H),3.06(s, 3H), 6.93(m, 1H), 7.06(m, 1H), 7.13(m, 1H), 7.90(m, 4H).IR(cm⁻¹): 2973, 2926, 1696, 1624, 1404, 1319, 1149, 959, 769, 552. 2053-Cl, mp: 120-123° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 4-Cl 1.54(s, 3H),1.97(m, 2H), 3.09(s, 3H), 7.08(m, 1H), 7.44(m, 2H), 7.84(d, J=8.7Hz,2H), 7.98(d, J=9.0Hz, 2H). IR(cm⁻¹): 2875, 2930, 1696, 1620, 1406, 1319,1150, 957, 769, 730, 552. 206 3- mp: 110-111° C. NMR: δ 0.96(t, J=7.5Hz,3H), CHF₂ 1.56(s, 3H), 1.97(m, 2H), 3.07(s, 3H), 6.63(t, J=56.4Hz, 1H),7.36(m, 1H), 7.47(m, 3H), 7.83(d, J=8.4Hz, 2H), 7.95(d, J=8.7Hz, 2H).IR(cm⁻¹): 2976, 2931, 1697, 1624, 1594, 1319, 1150, 1028, 769, 552. 2074-Cl mp: 62-63° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H),1.95-1.99(m, 2H), 3.08(s, 3H), 7.20-7.23(m, 2H), 7.35-7.38(m, 2H),7.83-7.86(m, 2H), 7.94-7.97(m, 2H). IR(cm⁻¹): 1696, 1588, 1319, 1150,1090, 968, 769, 552. 208 4-CF₃ mp: 56-57° C. NMR: δ 0.96(t, J=7.5Hz,3H), 1.56(s, 3H), 1.97-2.01(m, 2H), 3.09(s, 3H), 7.40-7.42(m, 2H),7.63-7.65(m, 2H), 7.82-7.85(m, 2H), 7.96-7.99(m, 2H). IR(cm⁻¹): 2978,2932, 1696, 1623, 1326, 1151, 1071, 846, 771, 552. 209 4- mp: 89-90° C.NMR: δ 0.95(t, J=7.5Hz, 3H), OCF₃ 1.55(s, 3H), 1.95-2.00(m, 2H), 3.09(s,3H), 7.25-7.33(m, 4H), 7.83-7.86(m, 2H), 7.95-7.98(m, 2H). IR(cm⁻¹):2976, 2931, 1697, 1567, 1259, 1150, 769, 552. 210 4-Cl, mp: 58-59° C.NMR: δ 0.95(t, J=7.5Hz, 3H), 3-F 1.55(s, 3H), l.98(m, 2H), 3.10(s, 3H),6.99(m, 1H), 7.14(m, lH), 7.40(m, 1H), 7.85(d, J=8.7Hz, 2H), 7.99(d,J=8.7Hz, 2H). IR(cm⁻¹): 2930, 17l5, 1698, 1622, 1403, 1319, 1150, 1074,959, 858, 768, 552. 211 4-F, NMR: δ 0.96(t, J=7.5Hz, 3H), 1.54(s, 3H),1.99(m, 2-Me 2H), 2.11(d, J=2.1Hz, 3H), 3.04(s, 3H), 7.00(m, 3H),7.74(d, J=8.4Hz, 2H), 7.90(d, J=8.lHz, 2H). IR (cm⁻¹): 2976, 2929, 1696,1612, 1564, 1320, 1246, 1160, 958, 769, 730, 551. 212 5-F, NMR: δ0.95(t, J=7.2Hz, 3H), 1.55(s, 3H), 1.98(m, 2-Me 2H), 2.35(s, 3H),3.06(s, 3H), 6.97(m, 1H), 7.19(m, 2H), 7.84(d, J=8.4Hz, 2H), 7.93(m,J=8.1Hz, 2H). IR(cm⁻¹): 2977, 2930, 1697, 1632, 1503, 1405, 1320, 1150,958, 771, 552. 213 3- mp: 133-134° C. NMR: δ 0.96(t, J=7.2Hz, 3H), OMe,1.54(s, 3H), l.96(q, J=8.lHz, 2H), 3.07(s, 3H), 4-OMe 3.82(s, 3H),3.91(s, 3H), 6.80(m, 2H), 6.87(m, 1H), 7.91(m, 4H). IR(cm⁻¹): 2974,2933, 1696, 1592, 1516, 1319, 1260, 1150, 1027, 770, 552. 214 3-F, mp:158-160° C. NMR: δ 0.94(t, J=7.2Hz, 3H), 4-OMe 1.53(s, 3H), 1.96(m, 2H),3.09(s, 3H), 3.92(s, 3H), 7.01(m, 3H), 7.86(d, J=8.4Hz, 2H), 7.96(m,J=8.4Hz, 2H). IR(cm⁻¹): 2932, 1697, 1519, 1318, 1270, 1149, 1024, 768,552. 215 3-CF₃, mp: 92-93° C. NMR: δ 0.98(t, J=7.5Hz, 3H), 5-CF₃ 1.58(s,3H), 2.01(m, 2H), 3.08(s, 3H), 7.76(s, 2H), 7.82(m, 3H), 8.01(m, 2H).IR(cm⁻¹): 2979, 2934, 1698, 1628, 1593, 1407, 1282, 1150, 1138, 959,896, 772, 704, 552. 216 3-Cl, mp: 188-190° C. NMR: δ 0.95(t, J=7.5Hz,3H), 5-Cl 1.54(s, 3H), 1.97(q, J=7.8Hz, 2H), 3.10(s, 3H), 7.17(m, 2H),7.35(m, 1H), 7.84(d, J=8.7Hz, 2H), 8.00(d, J=8.1Hz, 2H). IR(cm⁻¹): 2974,2931, 1696, 1596, 1559, 1319, 1150, 801, 551. 217 4- mp: 58-59° C. NMR:δ 0.94(t, J=7.5Hz, 3H), OMe, 1.53(s, 3H), 1.96(m, 2H), 2.26(s, 6H),3.07(s, 3H), 3,5-di- 3.75(s, 3H), 6.90(s, 2H), 7.90(m, 4H). IR(cm⁻¹): Me2974, 2930, 1688, 1622, 1591, 1330, 1149, 1014, 850, 769, 552. 2183,4,5- mp: 137-138° C. NMR: δ 0.96.(t, J=7.2Hz, 3H), tri- 1.54(s, 3H),1.97(m, 2H), 3.06(s, 3H), 3.76(s, 6H), OMe 3.87(s, 3H), 6.45(s, 2H),7.93(m, 4H). IR(cm⁻¹); 2973, 2934, 1696, 1582, 1394, 1321, 1149, 1126,770, 552.

Compounds of Example 219˜Example 226 were prepared according toprocedures similar to the synthetic procedure in Example 34.

EXAMPLE 219˜EXAMPLE 226

Example AR Melting point & spectral data 219 3-(6-methyl- NMR: δ 0.96(t,J=7.5Hz, 3H), 1.56(s, 3H), pyridyl) 1.98(q, J=3.6Hz, 2H), 2.59(s, 3H),3.08(s, 3H), 7.23(d, J=8.1Hz, 1H), 7.65(dd, J=8.1, 1.8Hz, 1H),7.83-7.86(m, 2H), 7.95-7.98(m, 2H), 8.33(d, J=1.8Hz, 1H). IR(cm⁻¹):2927, 1696, 1590, 1406, 1318, 1150, 769, 550. 220 3-Thienyl NMR: δ0.94(t, J=7.5Hz, 3H), 1.53(s, 3H), 1.98(m, 2H), 3.10(s, 3H), 6.93(m,1H), 7.31(m, 1H), 7.51(m, 1H), 7.92(d, J=8.7Hz, 2H), 7.99(d, J=9.0Hz,2H). IR(cm⁻¹): 3106, 2975, 2929, 1696, 1621, 1447, 1316, 1148, 959, 852,770, 552. 221 2-Furanyl mp: 138-139° C. NMR: δ 0.93(t, J=7.5Hz, 3H),1.52(s, 3H), 1.95(m, 2H), 3.11(s, 3H), 6.51(m, 1H), 6.89(m, 1H), 7.37(m,1H), 8.02(m, 4H). IR(cm⁻¹): 2976, 2930, 1701, 1642, 1545, 1409, 1317,1149, 1090, 1069, 958, 875, 770, 730, 552. 222 2-Benzo[b]- mp: 68-69° C.NMR: δ 0.97(t, J=7.2Hz, 3H), thienyl 1.54(s, 3H), 1.99(m, 2H), 3.10(s,3H), 7.33(m, 2H), 7.50(s, 1H), 7.76(m, 2H), 8.01(s, 4H). IR (cm⁻¹):2925, 2866, 1701, 1620, 1457, 1317, 1148, 957, 762, 760, 551. 2232-Benzo[b]- mp: 177-178° C. NMR: δ 0.96(t, J=7.5Hz, furanyl 3H), 1.54(s,3H), 1.98(m, 2H), 3.13(s, 3H), 7.28(m, 4H), 7.60(m, 1H), 8.07(m, 4H). IR(cm⁻¹): 2927, 1702, 1539, 1454, 1318, 1149, 959, 766, 747, 655, 551. 2242-Thienyl mp: 112-114° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H),1.96(m, 2H), 3.10(s, 3H), 7.06(m, 1H), 7.11(m, 1H), 7.36(m, 1H), 7.99(m,4H). IR(cm⁻¹): 3100, 2975, 2929, 1700, 1619, 1317, 1149, 770, 552. 2252-(5- NMR: δ 0.93(t, J=7.5Hz, 3H), 1.52(s, 3H), Methyl- 1.99(m, 2H),2.48(s, 3H), 3.10(s, 3H), 6.70(m, thienyl) 1H), 6.91(d, J=3.6Hz, 1H),8.00(m, 4H). IR (cm⁻¹): 2973, 2924, 1701, 1318, 1140, 769, 551. 226 5-NMR: δ 0.98(t, J=7.5Hz, 3H), 1.58(s, 3H), Pyrimidinyl 2.02(m, 2H),3.10(s, 3H), 7.83(d, J=8.7Hz, 2H), 8.02(d, J=8.7Hz, 2H), 8.70(s, 2H),9.18(s, 1H).

Compounds of Example 227˜Example 236 were synthesized by proceduressimilar to the synthetic procedure in Step 4 of Example 43.

EXAMPLE 227˜Example 236

Example R Melting point & spectral data 227 4-F mp: 129-130° C. NMR: δ0.94(t, J=7.5Hz, 3H), 1.54(s, 3H), 1.96(m, 2H), 4.90(br s, 2H), 7.08(dd,J=9.0Hz, 8.4Hz, 2H), 7.24(dd, J=9.0, 5.7Hz, 2H), 7.78(d, J=8.4Hz, 2H),7.92(d, J=8.4Hz, 2H). IR (cm⁻¹): 3339, 3261, 1682, 1619, 1511, 1343,1161. 228 3-F mp: 176-177° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H),1.97(m, 2H), 4.90(br s, 2H), 7.04(m, 3H), 7.35(m, 1H), 7.79(d, J=8.7Hz,2H), 7.93(d, J=8.4Hz, 2H) IR(cm⁻¹): 3253, 1689, 1620, 1343, 1160. 2293-Me mp: 115-116° C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.53(s, 3H), 1.96(m,2H), 2.34(s, 3H), 4.97(br s, 2H), 6.99(d, J=7.2Hz, 1H), 7.13(m, 2H),7.25(m, 1H), 7.80(d, J=8.7Hz, 2H), 7.89(d, J=9.0Hz, 2H). IR(cm⁻¹): 3387,3249, 1683, 1617, 1343, 1160. 230 3-Cl mp: 144-145° C. NMR: δ 0.95(t,J=7.5Hz, 3H), 1.54(s, 3H), 1.97(m, 2H), 4.95(br s, 2H), 7.13(m, 1H),7.30(m, 3H), 7.79(d, J=8.4Hz, 2H), 7.93(d, J=8.1Hz, 2H). IR(cm⁻¹): 3336,3258, 1683, 1615, 1342, 1161. 231 4-Cl mp: 115-116° C. NMR: δ 0.94(t,J=7.5Hz, 3H), 1.54(s, 3H), 1.96(m, 2H), 4.89(br s, 2H), 7.21(d, J=8.7Hz, 2H), 7.36(d, J=8.7Hz, 2H), 7.79(d, J=8.7Hz, 2H), 7.93(d, J=8.1Hz,2H). IR(cm⁻¹): 3237, 1682, 1615, 1586, 1339, 1161. 232 3-CF₃ mp: 77-78°C. NMR: δ 0.96(t, J=7.5Hz, 3H), 1.56(s, 3H), 1.98(m, 2H), 5.06(br s,2H), 7.47(m, 2H), 7.58(m, 2H), 7.77(d, J=9.0Hz, 2H), 7.93(d, J=8.7Hz,2H). IR(cm⁻¹): 3347, 3257, 1685, 1621, 1393, 1329, 1163. 233 4-CF₃ mp:79-80° C. NMR: δ 0.96(t, J=7.5Hz, 3H), 1.56(s, 3H), 1.98(m, 2H), 5.04(brs, 2H), 7.40(d, J=8.1Hz, 2H), 7.63(d, J=8.4Hz, 2H), 7.77(d, J=8.1Hz,2H), 7.94(d, J=8.4Hz, 2H). IR(cm⁻¹): 3336, 3254, 1686, 1621, 1392, 1164.234 3-F, mp: 206-207° C. NMR: δ 0.94(t, J=7.5Hz, 3H), 5-F 1.54(s, 3H),1.97(m, 2H), 4.91(br s, 2H), 6.81(m, 3H), 7.79(d, J=8.7Hz, 2H), 7.97(dJ=8.7Hz, 2H). IR(cm⁻¹): 3256, 1691, 1596, 1160. 235 3-F, mp: 157-158° C.NMR: δ 0.94(t, J=7.5Hz, 3H), 4-F 1.54(s, 3H), 1.96(m, 2H), 4.92(br s,2H), 6.98(m, 1H), 7.15(m, 2H), 7.78(d, J=8.4Hz, 2H), 7.95(d, J=8.7Hz,2H). IR(cm⁻¹): 3222, 1692, 1609, 1518, 1342, 1161. 236 3-OMe mp: 69-70°C. NMR: δ 0.95(t, J=7.5Hz, 3H), 1.54(s, 3H), 1.97(m, 2H), 3.78(s, 3H),4.93(br s, 2H), 6.82(m, 2H), 6.88(m, 1H), 7.27(m, 1H), 7.79(d, J=9.0Hz,2H), 7.90(d, J=9.0Hz, 2H). IR(cm⁻¹): 3339, 3253, 1692, 1617, 1344, 1259,1161.

EXAMPLE 237

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(2-furanyl)-2-methyl-3(2H)-furanone

5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-iodo-2-methyl-3(2H)-furanone wascoupled with 2-furanboronic acid according to a procedure similar to theprocedure in Example 44. mp: 154-155° C. NMR: δ0.92 (t, J=7.5 Hz, 3H),1.52 (s, 3H), 1.95 (m, 2H), 5.03 (br s, 2H), 6.51 (dd, J=3.0, 1.8 Hz,1H), 6.87 (d, J=3.0 Hz, 2H), 7.37 (d, J=1.5Hz, 1H), 7.94 (d, J=8.7 Hz,2H), 8.02 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 3347, 3257, 1692, 1545, 1341,1164.

Compounds of Example 238˜Example 254 were prepared by procedures similarto the synthetic procedure in Step 6 of Example 47.

EXAMPLE 238˜EXAMPLE 254

Example R Melting point & spectral data 238 3-F Mp: 131-132° C. NMR: δ0.93(t, J=7.5Hz, 6H), 1.99(q, J=7.5Hz, 4H), 3.08(s, 3H), 7.03(m, 3H),7.33(m, 1H), 7.85(d, J=8.7Hz, 2H), 7.96(d, J=8.7Hz, 2H). IR(cm⁻¹): 2972,1693, 1622, 1409, 1318, 1143. 239 3-Me Mp: 95-96° C. NMR: δ 0.93(t,J=7.5Hz, 6H), 1.98(q, J=7.5Hz, 4H), 2.35(s, 3H), 3.07(s, 3H), 6.99(m,1H), 7.10(m, 1H), 7.16(m, 1H), 7.27(m, 1H), 7.87(d, J=8.7Hz, 2H),7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 2972, 1694, 1622, 1319, 1150. 240 3-OMeMp: 80-81° C. NMR: δ 0.93(t, J=7.5Hz, 6H), 1.97(q, J=7.5Hz, 4H), 3.07(s,3H), 3.78(s, 3H), 6.89(m, 1H), 6.90(m, 2H), 7.29(m, 1H), 7.88(d,J=8.4Hz, 2H), 7.94(d, J=8.7Hz, 2H). IR(cm⁻¹): 2972, 1694, 1622, 1403,1318, 1150. 241 3-CF₃ Mp: 73-74° C. NMR: δ 0.94(t, J=7.5Hz, 6H), 2.00(q,J=7.5Hz, 4H), 3.08(s, 3H), 7.48(m, 3H), 7.61(d, J=7.5Hz, 1H), 7.83(d,J=9.0Hz, 2H), 7.97(d, J=8.7Hz, 2H). IR(cm⁻¹): 2970, 1696, 1376, 1325,1218, 1150. 242 4-F Mp: 174-175° C. NMR: δ 0.93(t, J=7.5Hz, 6H), 1.98(q,J=7.5Hz, 4H), 3.08(s, 3H), 7.08(m, 2H), 7.24(m, 2H), 7.85(d, J=8.7Hz,2H), 7.95(d, J=8.7Hz, 2H). IR(cm⁻¹): 2975, 1694, 1592, 1391, 1321, 1150.243 4-Cl Mp: 144-145° C. NMR: δ 0.92(t, J=7.5Hz, 6H), 1.98(q, J=7.5Hz,4H), 3.02(s, 3H), 7.20(d, J=8.4Hz, 2H), 7.36(d, J=8.4Hz, 2H), 7.85(d,J=9.0Hz, 2H), 7.96(d, J=8.7Hz, 2H). IR(cm⁻¹): 2972, 1695, 1408, 1318,1150. 244 4-OMe Mp: 166-167° C. NMR: δ 0.92(t, J=7.5Hz, 6H), 1.96(q,J=7.5Hz, 4H), 3.07(s, 3H), 3.83(s, 3H), 6.92(d, J=9.0Hz, 2H), 7.17(d,J=8.7Hz, 2H), 7.88(d, J=8.7Hz, 2H), 7.94(d, J=8.7Hz, 2H). IR(cm⁻¹):2971, 1692, 1593, 1513, 1317, 1149. 245 4-Me Mp: 96-97° C. NMR: δ0.92(t, J=7.5Hz, 6H), 1.97(q, J=7.5Hz, 4H), 2.38(s, 3H), 3.07(s, 3H),7.13(d, J=8.1Hz, 2H), 7.29(d, J=8.1Hz, 2H), 7.86(d, J=9.0Hz, 2H),7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 2971, 1693, 1594, 1401, 1317, 1149. 2464-CF₃ Mp: 121-122° C. NMR: δ 0.94(t, J=7.5Hz, 6H), 2.00(q, J=7.5Hz, 4H),3.09(s, 3H), 7.40(d, J=8.4Hz, 2H), 7.64(d, J=8.1Hz, 2H), 7.85(d,J=8.4Hz, 2H), 7.98(d, J=9.0Hz, 2H). IR(cm⁻¹): 2973, 1697, 1622, 1392,1325, 1151. 247 3-F, 4-F Mp: 159-160° C. NMR: δ 0.92(t, J=7.5Hz, 6H),1.98(q, J=7.5Hz, 4H), 3.09(s, 3H), 6.96(m, 1H), 7.15(m, 2H), 7.85(d,J=8.7Hz, 2H), 7.98(d, J=9.0Hz, 2H). IR(cm⁻¹): 2972, 1696, 1516, 1318,1276, 1149. 248 3-F, 5-F Mp: 96-97° C. NMR: δ 0.92(t, J=7.5Hz, 6H),1.98(q, J=7.5Hz, 4H), 3.10(s, 3H), 6.80(m, 3H), 7.85(d, J=8.7Hz, 2H),7.80(d, J=8.4Hz, 2H). IR (cm⁻¹): 2972, 1697, 1318, 1150. 249 3-OMe, Mp:130-131° C. NMR: δ 0.93(t, J=7.5Hz, 6H), 4-OMe 1.97(q, J=7.5Hz, 4H),3.07(s, 3H), 3.82(s, 3H), 3.90(s, 3H), 6.77(m, 2H), 6.87(d, J=8.1Hz,1H), 7.90(d, J=8.7Hz, 2H), 7.95(d, J=8.7Hz, 2H). IR (cm⁻¹): 2973, 1694,1593, 1516, 1319, 1149. 250 4-n-Pr NMR: δ 0.92(t, J=7.5Hz, 6H), 0.96(t,J=7.5Hz, 3H), 1.65(m, 2H), 1.97(q, J=7.5Hz, 4H), 2.61(t, J=7.5Hz, 2H),3.07(s, 3H), 7.15(d, J=8.1Hz, 2H), 7.20(d, J=8.4Hz, 2H), 7.87(d,J=8.4Hz, 2H), 7.93(d, J=8.7Hz, 2H). IR(cm⁻¹): 2969, 1694, 1594, 1318,1150. 251 2-F, 4-F Mp: 165-166° C. NMR: δ 0.93(t, J=7.5Hz, 6H), 1.99(q,J=7.5Hz, 4H), 3.07(s, 3H), 6.87(m, 1H), 6.98(m, 1H), 7.27(m, 1H),7.84(d, J=8.7Hz, 2H), 7.96(d, J=9.0Hz, 2H). IR(cm⁻¹): 2972, 1695, 1593,1318, 1150. 252 4-t-Bu NMR: δ 0.92(t, J=7.5Hz, 6H), 1.33(s, 39H),1.98(q, J=7.5Hz, 4H), 3.08(s, 3H), 7.18(d, J=8.7Hz, 2H), 7.39(d,J=8.4Hz, 2H), 7.89(d, J=8.7Hz, 2H), 7.94(d, J=9.0Hz, 2H). IR(cm⁻¹):2965, 1694, 1502, 1318, 1250, 1149. 253 3-Me, Oil. NMR: δ 0.92(t,J=7.5Hz, 6H), 1.96(q, J=7.5Hz, 4-Me 4H), 2.25(s, 3H), 2.28(s, 3H),3.06(s, 3H), 6.92(dd, J=7.8, 1.8Hz, 1H), 7.05(d, J=0.9Hz, 1H), 7.13(d,J=7.8Hz, 1H), 7.88(d, J=9.0Hz, 2H), 7.93(d, J=8.7Hz, 1H). IR(cm⁻¹):2971, 1694, 1403, 1318, 1244, 1149. 254 3-Cl, Mp: 173-174° C. NMR: δ0.92(t, J=7.5Hz, 6H), 4-F 1.98(q, J=7.5Hz, 4H), 3.09(s, 3H), 7.09(m,1H), 7.16(t, J=8.7Hz, 1H), 7.36(dd, J=7.2, 2.1Hz, 1H), 7.85(d, J=8.7Hz,2H), 7.98(d, J=8.4Hz, 2H). IR (cm⁻¹): 2973, 1694, 1503, 1308, 1149.

Compounds of Example 255˜Example 259 were prepared by procedures similarto the synthetic procedure in Step 6 for Example 53.

EXAMPLE 255˜EXAMPLE 259

Example R Melting point & spectral data 255 3-Me Mp: 142-143° C. NMR: δ2.03(m, 6H), 2.10(m, 2H), 2.34(s, 3H), 3.06(s, 3H), 7.00(d, J=7.5Hz,1H), 7.14(m, 1H), 7.26(m, 2H) 7.83(d, J=9Hz, 2H), 7.92(m, J=8.7Hz, 2H).IR(cm⁻¹): 2962, 1693, 1620, 1403, 1150, 958, 770. 256 3-F, 5-F mp:127-128° C. NMR: δ 2.03(m, 6H), 2.16(m, 2H), 3.09(s, 3H), 6.80(m, 1H),6.83(m, 2H), 7.82(d, J=8.7Hz, 2H), 7.98(d, J=8.7Hz, 2H). IR(cm⁻¹): 2962,1702, 1626, 1591, 1393, 1287, 1197, 987. 257 2-F mp: 120-121° C. NMR: δ2.05(m, 6H), 2.17(m, 2H), 3.06(s, 3H), 7.09(m, 1H), 7.24(m, 1H), 7.38(m,1H), 7.82(m, 2H) 7.83(m, 2H). IR(cm⁻¹): 2960, 1696, 1594, 1404, 1319,1150. 258 4-F mp: 109-113° C. NMR: δ 2.03(m, 6H), 2.16(m, 2H), 3.08(s,3H), 7.08(m, 2H), 7.28(m, 2H), 7.81(m, 2H), 7.85(m, 2H). IR(cm⁻¹): 2960,1696, 1594, 1404, 1319, 1150. 259 3-F mp: 158-160° C. NMR: δ 2.03(m,8H), 2.17(m, 2H), 3.08(s, 3H), 7.06(d, J=8.4Hz, 2H), 7.35(d, J=8.4Hz,2H), 7.82(d, J=8.4Hz, 2H), 7.95(m, 2H). IR(cm⁻¹): 2961, 1695, 1621,1403, 1318, 1151, 770.

EXAMPLE 260

3-(3-Methylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-one

3-(3-Methylphenyl)-2-{4-(methylsulfonyl)phenyl}-1-oxa-spiro[4,5]dec-2-en-4-onewas prepared by a procedure similar to the synthetic procedure in Step 6of Example 56. mp: 154-155° C. NMR: δ1.82 (m, 10H), 2.34 (s, 3H), 3.06(s, 3H), 6.99 (d, J=8.4 Hz, 1H), 7.13 (m, 2H), 7.25 (m, 1H), 7.86 (m,2H), 7.93 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2934, 1693, 1621, 1403, 1147,1129, 716.

EXAMPLE 261

3-(3-Fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-oneStep 1 Preparation of 4-ethynyl-4-hydroxy-tetrahydro-(4H)-pyran

To 29.8 g of cerium(III) chloride, which was dried for 2 hours at 140°C. and 0.1 torr, was added dry 200 ml THF under argon. The suspensionwas stirred for 2 hours and then was cooled to −78° C. To the stirredcerium chloride solution, was added dropwise 48 ml of 25% lithiumacetylide/ethylene diamine in toluene over 30 minutes, which wasfollowed by dropwise addition of 10 g of tetrhydro-(4H)-pyran-4-one in100 ml THF [Tetrahedron Lett. 25, 4233 (1984)]. Then the reactionmixture was slowly warmed to room temperature and was stirred for 18hours. The reaction was quenched by adding a minimum amount of aqueoussaturated ammonium chloride, and the resulting insoluble material wasfiltered off through celite. The filtrate was concentrated in vacuo andthe resulting residue was extracted with brine and 200 ml ethylacetate.The organic layer was dried over anhydrous magnesium sulfate and themagnesium sulfate was filtered off. Then 2.6 g of4-ethynyl-4-hydroxy-tetrahydro-(4H)-pyran was obtained from the filtrateupon concentration. NMR: δ1.77-1.86 (m, 2H), 1.91-1.99 (m. 2H), 2.51 (t,J=6.0 Hz, 1H), 2.55 (s, 1H), 3.62-3.70 (m, 2H), 3.87-4.00 (m, 2H). IR(cm⁻¹): 3388, 2960, 2865, 2109, 1717, 1338, 1085, 840.

Step 2 Preparation of1-{4-(methylthio)phenyl}-4,4-{tetrahydro-(4H)-pyranylidenyl}-2-butyn-1,4-diol

To a stirred solution of 4-ethynyl-4-hydroxy-tetrahydro-(4H)-pyran (2 g)in 90 ml dry THF, was added slowly 21.8 ml of 1.6 M butyllithium inhexane at −78° C. The mixture was stirred for 50 minutes, which wasfollowed by addition of p-(methylthio)benzaldehyde (2.41 g). Then thereaction solution was allowed to warm slowly to room temperature and wasstirred for 2 hours. The reaction was stopped by adding 100 mlice/water, which was followed by extraction with 100 ml methylenechloride. The organic layer was dried over anhydrous magnesium sulfateand the magnesium sulfate was filtered off. The filtrate wasconcentrated under reduced pressure, and the resulting crude product waspurified by column chromatography (hexane/ethylacetate) to yield 2.3 gof1-{4-(methylthio)phenyl}-4,4-{tetrahydro-(4H)-pyranylidenyl}-2-butyn-1,4-diol.NMR: δ1.79-1.88 (m, 2H), 2.20-2.35 (m, 2H), 2.50 (s, 3H), 3.61-3.70 (m,2H), 3.83-3.88 (m, 2H), 4.40 (s, 1H), 5.49 (d, J=6Hz, 1H), 5.80 (s, 1H),7.27 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.4 Hz, 2H). IR (cm⁻¹): 3370, 2975,2863, 2209, 1633, 1426, 1180, 743.

Step 3: Preparation of4-hydroxy-1-{4-(methylthio)phenyl}-4,4-{4-tetrahydro-(4H)-pyranylidenyl}-2-butyn-1-one

A mixture of pyridinium dichromate (4.7 g) and 2.3 g of1-{4-(methylthio)-phenyl}-4,4-{4-tetrahydro-(4H)-pyranylidenyl}-2-butyn-1,4-diolin 120 ml dichloromethane was stirred for 22 hours at room temperature,which was followed by addition of 40 ml ether. The reaction mixture wasthen filtered through Florisil and the filtrate was concentrated invacuo. The crude product was purified by column chromatography(hexane/ethylacetate) to give 1.2 g of4-hydroxy-1-{4-(methylthio)-phenyl}-4,4-{4-tetrahydro-(4H)-pyranylidenyl}-2-butyn-1-one.NMR: δ1.93-1.99 (m, 2H), 1.98-2.15 (m, 2H), 2.52 (s, 1H), 2.54 (s, 3H),3.70-3.78 (m, 2H), 3.93-4.00 (m, 2H), 7.29 (d, J=9.0 Hz, 2H), 8.02 (d,J=9.0 Hz , 2H). IR (cm⁻¹): 3400, 2957, 2862, 2208, 1568, 1263, 840.

Step 4: Preparation of2-{4-(methylthio)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one

To 1.20 g of4-hydroxy-1-{4-(methylthio)phenyl}-4,4-{4-tetrahydro-(4H)-pyranylidenyl}-2-butyn-1-onein 170 ml ethanol, was added dropwise 0.48 g of diethylamine diluted in60 ml ethanol. The mixture was stirred for an hour at room temperature,which was followed by concentration under reduced pressure. Theresulting residue was extracted with water and dichloromethane (100ml×2) and the organic layer was dried over anhydrous magnesium sulfate.The magnesium sulfate was removed by filtration and the filtrate wasconcentrated in vacuo. The crude product was then purified by columnchromatography (hexane/ethylacetate) to give 0.6 g of2-{4-(methylthio)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one as a solid.mp: 135-138° C. NMR: δ1.58-1.63 (m, 2H), 2.07-2.18 (m, 2H), 2.55 (s,3H), 3.81-3.91 (m, 2H), 4.04-4.10 (m, 2H), 5.97 (s, 1H), 7.32 (d, J=9.0Hz, 2H), 7.75 (d, J=9.0 Hz, 2H). IR (cm⁻¹): 2954, 2860, 1691, 1598,1583, 1468, 1096.

Step 5: Preparation of2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one

To a stirred solution of2-{4-(methylthio)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one (0.6 g) in10 ml THF and 10 ml ethanol, was added 2.67 g of OXONE dissolved in 5 mlwater. The mixture was stirred for 26 hours at room temperature. Aftervolatile solvent was evaporated in vacuo, the aqueous solution wasextracted with dichloromethane. The organic layer was concentrated underreduced pressure and the resulting crude product was purified byrecrystallization from hexane/dichloromethane to give 0.55 g of2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one. mp:163-165° C. NMR: δ1.58-1.70 (m, 2H), 2.09-2.20 (m, 2H), 3.11 (s, 3H),3.82-3.92 (m, 2H), 4.04-4.14 (m, 2H), 6.16 (s, 1H), 8.05 (d, J=8.7 Hz,2H), 8.10 (d, J=8.7 Hz, 2H). IR (cm⁻¹): 2862, 1694, 1314, 1152, 961.

Step 6: Preparation of3-iodo-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one

A mixed solution of2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one (0.55g), [bis(trifluoroacetoxy)iodo]benzene (0.84 g) and iodine (0.45 g) in50 ml dichloromethane was stirred for 6 hours at room temperature. Thenthe reaction was quenched by adding 10 ml aqueous saturated sodiumthiosulfate. The organic layer was washed with brine and wasconcentrated under reduced pressure. The resulting crude product waspurified by column chromatography (hexane/ethylacetate) to afford 0.6 gof3-iodo-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one.mp: 210-213° C. NMR: δ1.60-1.72 (m, 2H), 2.11-2.44 (m, 2H), 3.12 (s,3H), 3.80-3.90 (m, 2H), 4.04-4.14 (m, 2H), 8.21 (d, J=9 Hz, 2H), 8.41(d, J=9 Hz, 2H). IR (cm⁻¹): 1690, 1580, 1146, 912, 744.

Step 7: Preparation of3-(3-fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-one

To a stirred solution of 120 mg of3-iodo-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-4-onein 5 ml toluene and 5 ml ethanol, were added at room temperature16 mg oftetrakis(triphenylphosphine)palladiumn(0), 0.3 ml of 2M aqueous sodiumcarbonate and 43 mg of 3-fluorobenzeneboronic acid. The reaction mixturewas stirred at 100° C. for 3 hours. The reaction mixture was purified bya procedure similar to the method used for Example 2 to give 84 mg of3-(3-fluorophenyl)-2-{4-(methylsulfonyl)phenyl}-1,8-dioxa-spiro[4,5]dec-2-en-one.mp: 164-166° C. NMR: δ1.70-1.75 (m, 2H), 2.15-2.26 (m, 2H), 3.09 (s,3H), 3.84-3.94 (m, 2H), 4.08-4.14 (m, 2H), 7.02-7.10 (m, 3H), 7.31-7.40(m, 1H), 7.86 (d, J=8.4 Hz, 2H), 7.97 (d, J=8.4 Hz, 2H). IR (cm⁻¹):2862, 1694, 1623, 1430, 1318, 1148, 1103, 770.

Compounds of Example 262 and Example 263 were prepared by followingprocedures similar to the synthetic procedure in Step 7 of Example 261.

EXAMPLE 262 and EXAMPLE 263

Example R Melting point & spectral data 262 H mp: 169-171° C. NMR: δ1.65-1.75(m, 2H), 2.10-2.26(m, 2H), 3.07(s, 3H), 3.81-3.94(m, 2H),4.05-4.14(m, 2H), 7.25-7.40(m, 5H), 7.86(d, J=8.4Hz, 2H), 7.95(d,J=8.4Hz, 2H). IR(cm⁻¹): 2860, 1690, 1317, 1146, 730. 263 3-Cl mp: 96-99°C. NMR: δ 1.66-1.75(m, 2H), 2.15-2.26(m, 2H), 3.09(s, 3H), 3.84-3.93(m,2H), 4.07-4.15(m, 2H), 7.12-7.15(m, 1H), 7.31(7.35(m, 3H), 7.85(d,J=8.7Hz, 2H), 7.98(d, J=8.7Hz, 2H). IR (cm⁻¹): 2861, 1692, 1317, 1147,1102, 732.

EXAMPLE 264

2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanoneStep 1: Preparation of1-{3-fluoro-4-(methylthio)phenyl}-2-phenyl-ethan-1-one

To a stirred solution of 1.5 ml 2-fluorothioanisole in 50 mldichloromethane, were added at 0° C. 1.2 g of aluminum chloride and 1 mlof phenylacetyl chloride. The reaction mixture was stirred for 12 hoursat the room temperature. Then the reaction was quenched by addingappropriate amount of ice and aqueous HCl in one portion. The quenchedmixture was extracted with dichloromethane (50 ml×3) and the organiclayer was washed with brine. The organic layer was dried over anhydrousmagnesium sulfate, which was followed by removal of the magnesiumsulfate by filtration. Then the filtrate was concentrated in vacuo andwas purified by recrystallization from methanol to yield 1.8 g of1-{3-fluoro-4-(methylthio)phenyl}-2-phenyl-ethan-1-one. mp: 71-72° C.NMR: δ2.50 (s, 3H), 4.22 (s, 2H), 7.20-7.33 (m, 6H), 7.64 (m, 1H), 7.77(m, 1H). Step 2: Preparation of2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone

To a stirred solution of1-{3-fluoro-4-(methylthio)phenyl}-2-phenyl-ethan-1-one (1.68 g) in 100ml dry THF, was added portion-wise at 0° C. 60% oil dispersion of sodiumhydride (270 mg). The reaction solution was stirred at the sametemperature for 1 hour. Then 1.2 ml of α-bromo-isobutyryl cyanidediluted in 25 ml dry THF was added dropwise to the stirred solution at0° C. The reaction mixture was stirred overnight while warming graduallyto room temperature. The solution was concentrated in vacuo, to whichwas added 50 ml water. The aqueous solution was extracted withdichloromethane (50 ml×3). The organic layer was concentrated in vacuoand purified by column chromatography (hexane/ethylacetate=6:1) to give1.21 g of2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone.NMR: δ1.55 (s, 6H), 2.48 (s, 3H), 7.26-7.39 (m, 7H), 7.67 (m, 1H), 7.81(m, 1H). IR (cm⁻¹): 1696, 1421, 1388, 1238.

Compounds of Example 265˜Example 272 were synthesized by followingprocedures similar to a series of procedures employed in the synthesisof Example 264.

EXAMPLE 265˜EXAMPLE 272

Example R Melting point & spectral data 265 2-F NMR: δ 1.57(s, 6H),2.48(s, 3H), 7.12(m, 2H), 7.25(m, 1H), 7.34(m, 4H). IR(cm⁻¹): 1700,1600, 1391, 1215, 1160. 266 4-F NMR: δ 1.54(s, 6H), 2.49(s, 3H), 6.90(d,J=10.8, Hz, 1H), 6.99(t, J=8.7Hz, 2H), 7.02(dd, J=8.4, 1.8Hz, 1H),7.26(m, 2H), 7.40(m, 1H). IR(cm⁻¹): 1699, 1618, 1388, 1147, 1049. 2672-Cl NMR: δ 1.58(s, 6H), 2.46(s, 3H), 7.09(t, J=7.8Hz, 1H), 7.26(m, 3H),7.34(m, 2H), 7.49(m, 1H). IR (cm⁻¹): 1694, 1616, 1426, 1384, 1299, 1234,1155. 268 3-Cl NMR: δ 1.55(s, 6H), 2.49(s, 3H), 7.43(t, J=8.1Hz, 2H),7.59(m, 2H), 7.34(m, 2H), 7.49(m, 1H). 269 3-Cl, NMR: δ 1.55(s, 6H),2.50(s, 3H), 7.15(dd, J=8.1, 4-Cl 1.5Hz, 2H), 7.36(m, 2H), 7.43(m, 1H),7.46(m, 1H). IR(cm⁻¹): 1694, 1611, 1369, 1298, 1218, 1154, 1052. 2702-F, NMR: δ 1.58(s, 6H), 2.47(s, 3H), 6.85(m, 2H), 6-F 6.99(m, 1H),7.26(m, 2H), 7.56(m, 1H). IR(cm⁻¹): 1707, 1612, 1468, 1383, 1002. 2713-F, mp: 77-78° C. NMR: δ 1.55(s, 6H), 2.51(s, 3H), 5-F 6.77(m, 1H),6.87(m, 2H), 7.16(dd, J=8.4, 7.5Hz, 1H), 7.34(m, 1H), 7.36(m, 1H).IR(cm⁻¹): 1697, 1623, 1427, 1386, 1312, 1204, 1119. 272 4-NO₂ mp:107-108° C. NMR: δ 1.58(s, 6H), 2.50(s, 3H), 7.15(dd, J=8.7, 7.2Hz, 1H),7.32(m, 1H), 7.35(m, 1H), 7.53(d, J=9.0Hz, 2H), 8.27(d, J=9.0Hz, 2H).IR(cm⁻¹): 1696, 1608, 1517, 1427, 1382, 1345, 1219, 1152.

EXAMPLE 273

2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone

To2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3((2H)-furanone(1.21 g: Example 264) dissolved in 150 ml 1:1:1 methanol/THF/water, wasadded 2.77 g of OXONE. The mixture was stirred at room temperature forfour hours. Then the volatile solvent was removed in vacuo and theresulting solution was diluted with 50 ml water. The aqueous solutionwas extracted with dichloromethane (30 ml×3). The organic layer wasconcentrated under reduced pressure and was purified by columnchromatography hexane/ethylacetate=4:1) to afford 520 mg of2,2-dimethyl-5-{3-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone as asolid. mp: 190-191° C. NMR: δ1.55 (s, 6H), 3.23 (s, 3H), 7.26 (m, 2H),7.38 (m, 3H), 7.56 (m, 2H), 7.92 (m, 1H). IR (cm⁻¹): 1700, 1427, 1324,1160, 1147. MS (FAB): 361 (m+1).

Compounds of Example 274˜Example 287 were synthesized by proceduressimilar to the procedure in Example 273.

EXAMPLE 274˜EXAMPLE 287

Example R Melting point & spectral data 274 2-F mp: 135-136° C. NMR: δ1.58(s, 6H), 3.22(s, 3H), 7.10(m, 1H), 7.24(m, 1H), 7.38(m, 2H), 7.54(m,2H), 7.92(dd, J=8.4, 7.2Hz, 1H). IR(cm⁻¹): 1701, 1600, 1387, 1325, 1146.275 3-F mp: 182-183° C. NMR: δ 1.57(s, 6H), 3.24(s, 3H), 7.02(m, 3H),7.36(m, 1H), 7.55(m, 1H), 7.56(m, 1H), 8.00(dd, J=8.1, 7.2Hz, 1H).IR(cm⁻¹): 1700, 1601, 1385, 1323, 1160. MS(FAB): 379(m + 1) 276 4-F mp:160-161° C. NMR: δ 1.50(s, 6H), 3.17(s, 3H), 7.03(t, J=8.7Hz, 2H),7.18(t, J=8.4Hz, 2H), 7.49(m, 2H), 7.87(t, J=7.8Hz, 1H). IR(cm⁻¹): 1700,1323, 1159, 1147. 277 2-Cl mp: 122-123° C. NMR: δ 1.60(s, 6H), 3.22(s,3H), 7.25(m, 1H), 7.38(m, 2H), 7.45(m, 1H), 7.49(m, 2H), 7.91(dd, J=6.3,1.5Hz, lH). IR(cm⁻¹): 1705, 1611, 1429, 1384, 1325, 1150, 1072. 278 3-Clmp: 108-109° C. NMR: δ 1.58(s, 6H), 3.25(s, 3H), 7.13(m, 1H), 7.32(m,3H), 7.56(m, 2H), 7.95(t, J=7.8Hz, 1H). IR(cm⁻¹): 1704, 1695, 1567,1490, 1384, 1325, 1219, 1159. MS(FAB): 395(m + 1) 279 4-Cl mp: 130-131°C. NMR: δ 1.57(s, 6H), 3.25(s, 3H), 7.23(m, 2H), 7.39(d, J=8.4Hz, 2H),7.57(m, 2H), 7.95(d, J=6.9Hz, 1H). IR(cm⁻¹): 1700, 1694, 1610, 1495,1406, 1323, 1247, 1159. 280 3-Cl, mp: 149-150° C. NMR: δ 1.57(s, 6H),3.26(s, 3H), 4-Cl 7.09(dd, J=8.7, 2.1Hz, 1H), 7.46(m, 2H), 7.57(m, 2H),7.98(dt, J=7.5, 1.5Hz, 1H). IR(cm⁻¹): 1705, 1486, 1324, 1159, 1072, 974.281 2-F, mp: 183-184° C. NMR: δ 1.58(s, 6H), 3.24(s, 3H), 4-F 6.89(m,1H), 7.02(m, 1H), 7.44(m, 1H), 7.53(m, 1H), 7.55(m, 1H), 7.96(dd, J=8.4,7.2Hz, 1H). IR (cm⁻¹): 1702, 1600, 1507, 1386, 1324, 1160, 1146. 2822-F, mp: 140-141° C. NMR: δ 1.59(s, 6H), 3.24(s, 3H), 5-F 7.08(m, 3H),7.53(m, 1H), 7.56(m, 1H), 7.96(dd, J=8.1, 7.2Hz, 1H). IR(cm⁻¹): 1705,1604, 1498, 1426, 1324, 1161, 1138. 283 2-F, mp: 113-115° C. NMR: δ1.60(s, 6H), 3.23(s, 3H), 6-F 7.00(m, 2H), 7.40(m, 1H), 7.55(d, J=9.6Hz,2H), 7.94(dd, J=7.5, 7.2Hz, 1H). IR(cm⁻¹): 1700, 1604, 1467, 1325, 1146.284 3-F, mp: 158-159° C. NMR: δ 1.57(s, 6H), 3.26(s, 3H), 4-F 7.00(m,1H), 7.18(m, 2H), 7.55(m, 1H), 7.56(m, 1H), 7.98(dd, J=8.4, 7.2Hz, 1H).IR(cm⁻¹): 1702, 1604, 1517, 1324, 1283, 1160, 1137. 285 3-F, mp:163-164° C. NMR: δ 1.57(s, 6H), 3.26(s, 3H), 5-F 6.84(m, 3H), 7.55(m,1H), 7.56(m, 1H), 7.99(dd, J=8.1, 7.2Hz, 1H). IR(cm⁻¹): 1720, 1592,1388, 1322, 1218, 1160, 1137. MS(FAB): 397(m + 1). 286 4-CF₃ mp:134-135° C. NMR: δ 1.59(s, 6H), 3.25(s, 3H), 7.42(d, 2H), 7.53(m, 1H),7.56(m, 1H), 7.66(d, 2H), 7.97(dd, J=8.4, 7.2Hz, 1H). IR(cm⁻¹): 1702,1603, 1386, 1325, 1162, 1069. 287 4-NO₂ mp: 173-174° C. NMR: δ 1.60(s,6H), 3.26(s, 3H), 7.49(d, J=8.1Hz, 2H), 7.52(m, 1H), 7.56(m, 1H),7.99(dd, J=7.8, 7.2Hz, 1H), 8.26(d, J=8.1Hz, 2H). IR(cm⁻¹): 1701, 1605,1518, 1324, 1220, 1160, 1140.

EXAMPLE 288

4-(aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone

To 200 mg of2,2-dimethyl-4-(4-nitrophenyl)-5-{3-fluoro-4-(methylsulfonyl)-phenyl}-3(2H)-furanone(Example 287) in 7 ml ethanol and 1 ml water, were added 0.5 mlconcentrated HCl and 0.2 g of iron powder. The mixture was stirred for12 hours at 70° C. After the reaction mixture was cooled to roomtemperature, the unreacted iron was filtered off. The filtrate wasconcentrated in vacuo and the residue was neutralized with 1 N aqueoussodium hydroxide, which was followed by extraction with 30 mldichloromethane. The organic layer was concentrated under reducedpressure and was purified by column chromatography(hexane/ethylacetate=1:1) to afford 102 mg of4-(4-aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 199-200° C. NMR: δ1.54 (s, 6H), 3.24 (s, 3H), 3.80 (brs, 2H), 6.71 (d, J=8.7 Hz, 2H), 7.06 (d, J=8.7 Hz, 2H), 7.61 (dd,J=10.5, 1.8 Hz, 1H), 7.64 (dd, J=8.4, 1.8 Hz, 1H), 7.92 (dd, J=8.1, 7.2Hz, 1H). IR (cm⁻¹): 3468, 3374, 1694, 1517, 1386, 1320, 1159, 1147.

EXAMPLE 289

4-{4-N-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl)-phenyl}-3(2H)-furanone

60 mg of4-(4-aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)-phenyl}-3(2H)-furanone(Example 288) was reacted at room temperature for 12 hours with 0.2 mlacetic anhydride in 10 ml dichloromethane and 0.5 ml triethylamine inthe presence of 10 mg of N,N-dimethylaminopyridine. The solvent wasevaporated off in vacuo and the residue was extracted with 30 ml waterand 30 ml dichloromethane. The organic layer was concentrated in vacuoand was purified by column chromatography (hexane/ethylacetate=1:1) toafford 38 mg of4-{4-N-(acetylamino)-phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 170-171° C. NMR: δ1.57 (s, 6H), 2.21 (s, 3H), 3.25 (s,3H), 7.23 (d, J=9.9 Hz, 2H), 7.56 (m, 3H), 7.60 (dd, J=8.4, 1.8 Hz, 1H),7.93 (dd, J=7.8, 7.2 Hz, 1H). IR (cm⁻¹): 3335, 1697, 1596, 1524, 1319,1159, 1147.

EXAMPLE 290

2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl)-4-(3-fluorophenyl)-3(2H)-furanone

To a stirred solution of(2,2-dimethyl)-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone(1.6 g) in 50 ml dichloromethane, which was prepared by a proceduresimilar to the procedure employed for Example 264, 1.25 g ofm-chloroperoxybenzoic acid at 0° C. The reaction solution was stirredfor one and half hours at the temperature, after which 30 ml 5% aqueoussodium bicarbonate was added and the solution was stirred for another 10minutes. Then the reaction mixture was concentrated in vacuo, and theresulting residue was extracted with 50 ml water and dichloromethane (30ml×3). The organic layer was concentrated in vacuo and was purified bycolumn chromatography (hexane/ethylacetate=1:1) to give 1.6 g of2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanoneas a solid. mp: 148-149° C. NMR: δ1.58 (s, 6H), 2.87 (s, 3H), 7.06 (m,3H), 7.36(m, 1H), 7.42 (dd, J=10.5, 1.8 Hz, 1H), 7.66 (dd, J=8.4, 1.8Hz, 1H), 7.87 (dd, J=8.1. 6.9 Hz, 1H). IR (cm⁻¹): 1700, 1623, 1420,1261, 1216, 1192, 1135, 1077.

Compounds of Example 291˜Example 299 were synthesized by followingprocedures similar to the procedure employed for the synthesis ofExample 290.

EXAMPLE 291˜EXAMPLE 299

Ex- ample R Melting point & spectral data 291 H Mp: 149-150°C. NMR:δ1.57(s, 6H), 2.85(s, 3H), 7.26- 7.44(m, 6H), 7.68(m, 1H), 7.83(dd,J=8.4, 6.9Hz, 1H). IR(cm⁻¹): 1699, 1414, 1150, 1079, 1062. 292 2-F NMR:δ1.58(s, 6H), 2.85(s, 3H), 7.10(m, 1H), 7.24(m, 1H), 7.40(m, 3H),7.62(dd, J=8.1, 1.5Hz, 1H), 7.84(dd, J=8.1, 7.4Hz, 1H). IR(cm⁻¹): 1700,1598, 1419, 1385, 1078. 293 4-F NMR: δ1.57(s, 6H), 2.86(s, 3H), 7.10(t,J=8.4Hz, 2H), 7.25(m, 1H), 7.39(m, 2H), 7.66(dd, J=8.1, 1.8Hz, 1H),7.86(m, 1H). IR(cm⁻¹): 1698, 1511, 1423, 1383, 1236. 294 2-Cl NMR:δ1.60(s, 6H), 2.89(s, 3H), 7.26(m, 1H), 7.37(m, 3H), 7.53(m, 2H),7.78(m, 1H). IR(cm⁻¹): 1703, 1625, 1565, 1469, 1384, 1153, 1077. 2953-Cl NMR: δ1.57(s, 6H), 2.87(s, 3H), 7.15(m, 1H), 7.33(m, 2H), 7.42(m,1H), 7.65(dd, J=8.1, 1.5Hz, 1H), 7.87(m, 3H). IR(cm⁻¹): 1702, 1621,1566, 1412, 1382, 1240, 1151, 1078. 296 3-Cl, NMR: δ1.57(s, 6H), 2.88(s,3H), 7.12(dd, J=8.4, 2.1 4-Cl Hz, 1H), 7.44(m, 3H), 7.66(d, J=8.4Hz,1H), 7.90(t, J= 7.8Hz, 1H). IR(cm⁻¹)1703, 1622, 1564, 1485, 1371, 1215,1151. 297 2-F, mp: 141-142°C. NMR: δ1.59(s, 6H), 2.86(s, 3H), 7.08 5-F(m, 3H), 7.42(dd, J=10.8, 1.5Hz, 1H), 7.62(dd, J=8.4, 1.8Hz, 1H),7.87(dd, J=8.1, 7.2Hz, 1H). IR(cm⁻¹): 1704, 1602, 1497, 1422, 1381,1213. 298 2-F, mp: 90-92°C. NMR: δ1.60(s, 6H), 2.85(s,3H), 7.00(m, 6-F2H), 7.42(m, 1H), 7.46(m, 1H), 7.63(m, 1H), 7.86(m, 1H). IR(cm⁻¹): 1707,1486, 1384, 1148, 1080, 1003. 299 3-F, mp: 138-139°C. NMR: δ1.57(s, 6H),2.88(s, 3H), 6.84 5-F (m, 3H), 7.41(dd,J=10.5, 1.8Hz, 1H), 7.65(dd,J=8.4, 1.2Hz, 1H), 7.90(dd, J=8.1, 6.9Hz, 1H). IR(cm⁻¹): 2985, 1702,1593, 1386, 1213, 1137, 1078.

EXAMPLE 300

5-{4(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

220 mg of2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone(Example 291) was stirred for 2 hours at 0° C. in 30 ml trifluoroaceticanhydride. The volatile material was removed in vacuo. And 30 ml of 1:1methanol and triethylamine was added to the resulting residue. Thesolution was then concentrated under reduced pressure. To the resultingresidue dissolved in 30 ml dichloromethane, was slowly added 5 ml aceticacid saturated with chlorine. The reaction mixture was stirred at roomtemperature for 5 minutes, which was followed by the removal of volatilematerials in vacuo. The resulting residue was dissolved in 30 mltoluene, which was concentrated again in vacuo. The residue was dilutedwith 30 ml THF and then reacted with 3 ml aqueous ammonia at roomtemperature overnight. The reaction solution was concentrated underreduced pressure, and the resulting residue was extracted with 30 mlwater and dichloromethane (30 ml×3). The organic layer was concentratedin vacuo and then was purified by column chromatography(hexane/ethylacetate=3:2) to yield 65 mg of5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone.NMR: δ1.57 (s, 6H), 5.11 (br s, 21H), 7.27 (m, 2H), 7.40 (m, 3H), 7.52(m, 2H), 7.86 (dd, J=8.1, 6.9 Hz, 1H). IR (cm⁻¹): 3404, 3227, 1685,1560, 1356, 1150. MS (FAB): 362 (m+1).

Compounds of Example 301 Example 313 were prepared by a proceduresimilar to the procedure used for the synthesis of Example 300.

EXAMPLE 301˜EXAMPLE 313

Ex- ample R Melting point & spectral data 301 2-F mp: 86-87°C. NMR:δ1.58(s, 6H), 5.20(br s, 2H), 7.11 (m, 1H), 7.25(m, 1H), 7.36(m, 2H),7.52(m, 2H), 7.86 (dd, J=8.1, 7.2Hz, 1H). IR(cm⁻¹): 3367, 3272, 1697,1598, 1352, 1173. 302 3-F mp: 178-179°C. NMR: δ1.57(s, 6H), 5.20(br s,2H), 7.04(m, 3H), 7.36(m, 1H), 7.50(m, 1H), 7.53(m, 1H), 7.89(dd, J=8.4,6.9Hz, 1H). IR(cm⁻¹): 3347, 3261, 1689, 1563, 1427, 1351, 1262, 1172.MS(FAB): 380(m+1). 303 4-F mp: 190-192°C. NMR: δ1.57(s, 6H), 5.19(br s,2H), 7.10(m, 2H), 7.25(t, J=8.1Hz, 2H), 7.50(m, 1H), 7.53(m, 1H),7.89(dd, J=8.4, 7.2Hz, 1H). IR(cm⁻¹): 3410, 3282, 1687, 1510, 1237,1173, 1150. 304 2-Cl mp: 122-123°C. NMR: δ1.60(s, 6H), 5.07(br s, 2H),7.25(m, 2H), 7.37(m, 2H), 7.42(m, 1H), 7.47(m, 1H), 7.86(dd, J=8.4Hz,1H). IR(cm⁻¹): 1692, 1623, 1611, 1565, 1428, 1353, 1224. 305 3-Cl mp:164-165°C. NMR: δ1.57(s, 6H), 5.11(br s, 2H), 7.13(m, 1H), 7.33(m, 3H),7.52(m, 2H), 7.90(t, J=7.8Hz, 1H). IR(cm⁻¹): 1692, 1608, 1566, 1353,1174, 1079. 306 4-Cl mp: 204-205°C. NMR: δ1.56(s, 6H), 5.10(br s, 2H),7.23(d, J=8.4Hz, 2H), 7.38(d, J=8.1Hz, 2H), 7.53(d, J= 9.3Hz, 2H),7.90(m, 1H). IR(cm⁻¹): 1689, 1620, 1495, 1410, 1351, 1172 307 3-Cl, mp:200-201°C. NMR: δ1.57(s, 6H), 5.14(br s, 2H), 4-Cl 7.09(dd, J=8.1,1.8Hz, 1H), 7.46(m, 2H), 7.52(m, 2H), 7.92(t, J=7.8Hz, 1H). IR(cm⁻¹):1697, 1615, 1481, 1352, 1292, 1153. 308 2-F, mp: 184-185°C. NMR:δ1.58(s, 6H), 5.10(br s, 2H), 4-F 6.88(m, 1H), 7.01(m, 1H), 7.34(m, 1H),7.49(m, 1H), 7.50(m, 1H), 7.90(dd, J=8.1, 7.2Hz, 1H). IR(cm⁻¹): 3368,3265, 1692, 1597, 13521219, 1173, 1149. 309 2-F, mp: 172-173°C. NMR:δ1.59(s, 6H), 5.16(br s, 2H), 5-F 7.08(m, 3H), 7.50(m, 2H), 7.89(dd,J=7.8, 7.2Hz, 1H). IR(cm⁻¹): 3350, 3264, 1698, 1602, 1499, 1426, 1217,1174. 310 2-F, mp: 186-188°C. NMR: δ1.59(s, 6H), 5.15(br s, 2H), 6-F6.98(m, 2H), 7.39(m, 1H), 7.49(m, 2H), 7.87(dd, J= 8.7, 7.2Hz, 1H).IR(cm⁻¹): 3348, 3260, 1702, 1602, 1467, 1275. 311 3-F, mp: 199-200°C.NMR: δ1.57(s, 6H), 5.10(br s, 2H), 4-F 7.00(m, 1H), 7.17(m, 1H), 7.50(m,1H), 7.53(m, 2H), 7.92(dd, J=7.5, 7.2Hz, 1H). IR(cm⁻¹): 3238, 1703,1603, 1410, 1351, 1219, 1172. 312 3-F, mp: 198-199°C. NMR: δ1.57(s, 6H),5.20(br s, 2H), 5-F 6.82(m, 3H), 7.50(m, 1H), 7.53(m, 1H), 7.93(dd,J=7.8, 7.2Hz, 1H). IR(cm⁻¹): 3255, 1697, 1594, 1391, 1219, 1172. 313 4-mp: 222-223°C. NMR: δ1.60(s, 6H), 5.13(br s, 2H), NO₂ 7.48(m, 1H),7.49(d, J=8.1Hz, 2H), 7.51(m, 1H), 7.94 (dd, J=8.1, 7.2Hz, 1H), 8.25(d,J=8.1Hz, 2H). IR(cm⁻¹): 3268, 1703, 1603, 1515, 1347, 1219.

EXAMPLE 314

2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone

1-{2-Fluoro-4-(methylthio)phenyl}-2-phenyl-ethan-1-one (675 mg), whichwas prepared by a procedure similar to Step 1 in Example 264, wasdissolved in 50 ml dry THF, to which was added 120 mg of sodium hydride.The reaction mixture was stirred for an hour at 0° C., which wasfollowed by dropwise addition of 0.35 ml α-bromoisobutyryl cyanidediluted with 20 ml THF. The reaction mixture was allowed to warm to roomtemperature and was stirred overnight. The reaction solvent was removedin vacuo and the resulting residue was extracted with 50 ml water anddichloromethane (30 ml×3). The organic layer was concentrated underreduced pressure and was purified by column chromatography(hexane/ethylacetate=6:1) to yield 353 mg of2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone.NMR: δ1.54 (s, 6H), 2.49 (s, 3H), 6.90 (dd, J=10.8, 1.8 Hz, 1H), 7.00(dd, J=8.4, 1.8 Hz, 1H), 7.22-7.29 (m, 5H), 7.40 (dd, J=8.4, 7.2 Hz,1H). IR (cm⁻¹): 1699, 1610, 1388, 1175, 1049.

Compounds of Example 315˜Example 320 were synthesized by proceduressimilar to the procedure in synthesis of Example 314.

EXAMPLE 315˜EXAMPLE 320

Ex- ample R Melting point & spectral data 315 3-Cl NMR: δ1.55(s, 6H),2.51(s, 3H), 6.91(m, 1H), 7.04(m, 1H), 7.136(m, 1H), 7.21(m, 3H),7.43(m, 1H). IR(cm⁻¹): 1696, 1615, 1381, 1217, 1148 316 3-F NMR:δ1.55(s, 6H), 2.51(s, 3H), 6.94(m, 4H), 7.06(m, 1H), 7.26(m, 1H),7.43(dd, J=8.4, 6.9Hz, 1H). IR(cm⁻¹): 2928, 1697, 1618, 1388, 1216,1194, 1080. 317 4-F NMR: δ1.55(s, 6H), 2.51(s, 3H), 6.90(dd, J=8.1, 1.8Hz, 1H), 6.95-7.05(m, 3H), 7.25(m, 1H), 7.42(dd, J=8.1, 7.2Hz, 2H).IR(cm⁻¹): 1698, 1592, 1381, 1223, 1045. 318 2-F, NMR δ1.57(s, 6H),2.49(s, 3H), 6.86-7.11(m, 5H), 7.47 5-F (dd, J=8.1, 7.5Hz, 1H). 319 3-F,Mp: 122-123°C. NMR: δ1.56(s, 6H), 2.53(s, 3H), 6.69 5-F (m, 1H), 6.85(m,2H), 6.94(dd, J=11.4, 2.1Hz, 1H), 7.08 (dd, J=8.4, 1.8Hz, 1H), 7.46(dd,J=8.4, 7.2Hz, 1H). IR(cm⁻¹)1699, 1611, 1383, 1206, 1119 320 2-F, NMR:δ1.58(s, 6H), 2.47(s, 3H), 6.90(m, 2H), 7.11(m, 6-F 1H), 7.37(m, 3H).IR(cm⁻¹): 1702, 1603, 1466, 1385, 1153.

EXAMPLE 321

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl)}-4-phenyl-3(2H)-furanone

305 mg of2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone(Example 314) was dissolved in 30 ml methanol, 20 ml TBF and 20 mlwater, to which 1.4 g of OXONE was added. The reaction mixture wasstirred overnight at room temperature. Then the solvent was removed invacuo and the resulting residue was extracted with 50 ml water anddichloromethane (30 ml×3). The organic layer was concentrated underreduced pressure and then was purified by column chromatography(hexane/acetate=3:2) to obtain 70 mg of2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanoneas a solid. mp: 175-176° C. NMR: δ1.57 (s, 6H), 3.10 (s, 3H), 7.22 (m,2H), 7.28 (m, 3H), 7.75 (dd, J=8.7, 1.8 Hz, 1H), 7.77 (m, 2H). IR(cm⁻¹): 1702, 1408, 1321, 1147. MS (FAB): 361 (m+1).

Compounds of Example 322 Example 326 were prepared by procedures similarto the synthetic procedure for Example 321.

EXAMPLE 322˜EXAMPLE 326

Ex- ample R Melting point & spectral data 322 3-Cl mp: 139-140°C. NMRδ1.58(s, 6H), 3.12(s, 3H), 7.05 (m, 1H), 7.25(m, 3H), 7.77(m, 3H).IR(cm⁻¹): 1701, 1409, 1320, 1232, 1117, 966 323 3-F mp: 157-158°C. NMR:δ1.58(s, 6H), 3.12(s, 3H), 6.97 (m, 3H), 7.26(m, 1H), 7.43(m, 1H),7.71(dd, J=9.0, 1.8 Hz, 1H), 7.796(m, 1H). IR(cm⁻¹): 1701, 1577, 1433,1308, 1117. 324 4-F mp: 150-152°C. NMR: δ1.59(s, 6H), 3.11(s, 3H),7.02(t, J=9.0Hz, 2H), 7.23(m, 2H), 7.71(dd, J=10.0, 1.5Hz, 1H), 7.79(d,J=5.7Hz, 1H), 7.81(d, J=1.5Hz, 1H). 325 2-F, mp: 150-151°C. NMR:δ1.60(s, 6H), 3.11(s, 3H), 6.96 5-F (m, 2H), 7.15(m, 1H), 7.69(dd,J=8.7, 1.8Hz, 1H), 7.81 (d, J=3.0Hz, 2H). IR(cm⁻¹)1707, 1499, 1321,1227. 326 3-F, mp: 118-119°C. NMR: δ1.57(s, 6H), 3.13(s, 3H), 6.77 5-F(m, 3H), 7.75(m, 1H), 7.82(m, 1H), 7.85(m, 1H). IR (cm⁻¹): 1703, 1626,1408, 1326, 1121.

EXAMPLE 327

2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone

To 241 mg of2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone(Example 314) dissolved in 50 ml dichloromethane, was added 138 mg of70% m-chloroperoxybenzoic acid. The mixture was stirred at 0° C. for 1.5hours, which was followed by addition of 30 ml 5% aqueous sodiumbicarbonate. Then the mixture was stirred for 10 minutes and thevolatile material was removed in vacuo. The resulting residue wasextracted with 50 ml water and dichloromethane (30 ml×3). The organiclayer was concentrated under reduced pressure, and then was purified bycolumn chromatographic separation (hexane/ethylacetate=1:1) to afford187 mg of2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanoneas a solid. mp: 149-150° C. NMR: δ1.55 (s, 6H), 2.78 (s, 3H), 7.26 (m,5H), 7.47 (m, 2H), 7.69 (dd, J=8.4, 6.6 Hz, 2H). IR (cm⁻¹): 1700, 1621,1380, 1223, 1161, 1075.

Compounds of Example 328˜Example 331 were synthesized according to aprocedure similar to the synthetic procedure employed for Example 327.

EXAMPLE 328˜EXAMPLE 331

Example R Melting point & spectral data 328 3-F mp: 125-126° C. NMR: δ1.54 (s, 6H), 2.79 (s, 3H), 7.01 (m, 3H), 7.25 (m, 2H), 7.49 (m, 1H),7.78 (m, 1H). IR (cm⁻¹): 1701, 1577, 1433, 1308, 1117. 329 4-F NMR: δ1.57 (s, 6H), 2.79 (s, 3H), 6.99 (t, J=8.7 Hz, 2H), 7.22 (dd, J=9.0, 5.4Hz, 2H), 7.46 (d, J=8.4 Hz, 2H), 7.70 (dd, J=8.1, 6.0 Hz, 1H). IR(cm⁻¹): 1700, 1625, 1593, 1512, 1386, 1224. 330 3-F, mp: 114-115° C.NMR: δ 1.57 (s, 6H), 2.80 (s, 3H), 6.78 5-F (m, 1H), 6.82 (m, 2H), 7.49(m, 2H), 7.73 (dd, J=8.7, 6.0 Hz, 1H). IR (cm⁻¹): 1702, 1582, 1390,1314, 1120. 331 2-F, NMR: δ 1.62 (s, 6H), 2.77 (s, 3H), 7.00 (m, 2H),7.42 (m, 6-F 2H), 7.63 (dd, J=8.1, 1.5 Hz, 1H), 7.86 (dd, J=8.6, 7.2 Hz,1H). IR (cm⁻¹): 1707, 1606, 1384.

EXAMPLE 332

5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

154 mg of2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone(Example 327) was stirred in 30 ml trifluoroacetic anhydride at 0° C.for 2 hours. Then the volatile material was removed in vacuo, to whichwas added 50 ml of 1:1 methanol and triethylamine. The solution wasstirred for 20 minutes at 0° C. and the solvent was removed underreduced pressure. The resulting residue was dissolved in 40 mldichloromethane, which was followed by dropwise addition of 15 ml aceticacid saturated with chlorine. The reaction solution was stirred for 20minutes at 0° C. Then the solvent and unreacted chlorine were removed invacuo. The resulting residue was dissolved in 30 ml toluene and thetoluene was evaporated off under reduced pressure. Then the resultingresidue was dissolved in 40 ml THF and reacted with 5 ml ammonia waterby stirring overnight. The solvent was removed in vacuo and theresulting residue was extracted with 30 ml water and dichloromethane (30ml×3). The organic layer was concentrated in vacuo and was then purifiedby column chromatography (hexane/ethylacetate=3:2) to give 42 mg of5-{4-(aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 79-81° C. NMR: δ1.58 (s, 6H), 5.01 (br s, 2), 7.20-7.31(m, 5H), 7.69-7.76 (m, 3H). IR (cm⁻¹): 3340, 3274, 1591, 1526, 1328. MS(FAB): 362 (m+1).

Compounds of Example 333˜Example 335 were prepared by procedures similarto the method used for Example 332.

EXAMPLE 333˜EXAMPLE 335

Ex- ample R Melting point & spectral data 333 3-F mp: 168-170°C. NMR:δ1.55(s, 6H), 5.28(br s, 2H), 6.95(m, 3H), 7.25(m, 1H), 7.65(m, 2H),7.75(m, 1H). IR (cm⁻¹): 3344, 3261, 1695, 1626, 1407, 1349. MS(FAB):380(m+1). 334 4-F mp: 95-97°C. NMR: δ1.57(s, 6H), 5.11(br s, 2H), 7.02(m, 2H), 7.18(m, 2H), 7.76(m, 3H). IR(cm⁻¹): 3366, 3268, 1700, 1625,1511, 1230, 1164. MS(FAB): 380(m+1). 335 3-F, mp: 185-187°C. NMR:δ1.57(s, 6H), 5.10(br s, 2H), 5-F 6.77(m, 3H), 7.71(m, 2H), 7.80(m, 1H).IR(cm⁻¹): 3327, 3249, 1698, 1624, 1316, 1161. MS(FAB): 398(m+1)

EXAMPLE 336

5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

To a stirred solution of1-{3-bromo4(methylthio)phenyl}-2-phenyl-ethan-1-one (1.54 g) in 50 mlTHF, was added 232 mg of 60% oil dispersion of sodium hydride. Themixture was stirred for 1 hour at 0° C., which was followed by dropwiseaddition of 1.1 ml α-bromoisobutyryl cyanide diluted in 20 ml THF. Thereaction mixture was then slowly warmed to room temperature and wasstirred overnight. The solvent was removed in vacuo and the resultingresidue was extracted with 50 ml water and dichloromethane (30 ml×3).The organic layer was concentrated under reduced pressure and waspurified by column chromatography (hexane/ethylacetate=6:1) to yield 1.1g of5-{3-bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone.NMR: δ1.55 (s, 6H), 2.47 (s, 3H), 6.99 (d, J=8.7 Hz, 1H), 7.32 (m, 5H),7.48 (dd, J=8.7, 2.1 Hz, 1H), 7.88 (d, J=1.8 Hz, 1H).

Compounds of Example 337˜Example 340 were prepared by procedures similarto the procedures of Example 336.

EXAMPLE 337˜EXAMPLE 340

Ex- ample R Melting point & spectral data 337 3-Cl NMR: δ1.55(s, 6H),2.49(s, 3H), 7.02(d, J=8.7Hz, 1H), 7.18(m, 1H), 7.32(m, 3H), 7.46(dd,J=7.2, 1.8Hz, 1H), 7.88(d, J=2.1Hz, 1H). IR(cm⁻¹): 1695, 1609, 1389,1239. 338 3-F mp: 108-109°C. NMR: δ1.55(s, 6H), 2.47(s, 3H), 7.06 (m,4H), 7.34(m, 1H), 7.49(dd, J=7.2, 1.8Hz, 1H), 7.87 (d, J=1.8Hz, 1H).IR(cm⁻¹): 2983, 1696, 1599, 1391, 1258, 1195. 339 2-F, NMR: δ1.57(s,6H), 2.47(s, 3H), 7.04(m, 4H), 7.44(dd, 5-F J=8.7, 1.8Hz, 1H),7.86(d,J=1.5Hz, 1H). IR(cm⁻¹) 1699, 1595, 1417, 1250. 340 3-F, mp:115-116°C. NMR: δ1.55(s, 6H), 2.50(s, 3H), 6.79 5-F (m, 1H), 6.86(m,2H), 7.05(d, J=8.4, 1H), 7.47(dd, J= 8.4, 1.8Hz, 1H), 7.87(d, J=1.8Hz,1H). IR(cm⁻¹): 2925, 1689, 1604, 1391, 1120.

EXAMPLE 341

5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

350 mg of5-{3-bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 336), dissolved in 50 ml methanol, 50 ml THF and 50 ml water,was reacted with 1.5 g of OXONE by stirring at room temperature for 15hours. Then the solvent was removed in vacuo and the resulting residuewas extracted with 50 ml water and dichloromethane (30 ml×3). Theorganic layer was concentrated under reduced pressure and was purifiedby column chromatography (hexane/ethylacetate=3:2) to yield 173 mg of5-{3-bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 154-155° C. NMR: δ1.58 (s, 6H), 3.29 (s, 3H), 7.26 (m,3H), 7.38 (m, 2H), 8.07 (d, J=1.8 Hz, 1H), 8.10 (d, J=8.1 Hz, 2H). IR(cm⁻¹): 1698, 1585, 1318, 1150.

Compounds of Example 342˜Example 345 were synthesized by followingprocedures similar to the method employed for Example 341.

EXAMPLE 342˜EXAMPLE 345

Ex- ample R Melting point & spectral data 342 3-Cl NMR: δ1.59(s, 6H),3.32(s, 3H), 7.14(m, 3H), 7.35(m, 1H), 7.69(dd, J=8.4, 1.8Hz, 1H),8.08(d, J= 1.8Hz, 1H), 8.16(d, J=8.4Hz, 1H). IR(cm⁻¹): 1700, 1388, 1320,1151. 343 3-F mp: 133-134°C. NMR: δ1.57(d, 6H), 3.30(s, 3H), 7.03 (m,3H), 7.33(m, 1H), 7.69(dd, J=8.4, 1.8Hz, 1H), 8.05 (d, J=1.5Hz, 1H),8.14(d, J=8.4Hz, 1H). IR(cm⁻¹): 2931, 1700, 1586, 1390, 1312, 1151.MS(FAB): 441(m+ 2), 439(m). 344 2-F, NMR: δ1.59(s, 6H), 3.30(s, 3H),7.09(m, 3H), 7.68(dd, 5-F J=8.4, 1.8Hz, 1H), 8.06(d, J=1.8Hz, 1H),8.16(d, J= 8.4Hz, 1H). IR(cm⁻¹): 1704, 1495, 1387, 1151. 345 3-F, mp:194-195°C. NMR: δ1.58(s, 6H), 3.32(s, 3H), 6.83 5-F (m, 3H), 7.70(dd,J=8.4, 1.8Hz, 1H), 8.06(d, J=1.8Hz, 1H), 8.18(d, J=8.1Hz, 1H). IR(cm⁻¹):1702, 1627, 1377, 1120.

EXAMPLE 346

5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

391 mg of5-{3-bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 336) dissolved in 50 ml dichloromethane was stirred at 0° C.for 50 minutes in the presence of 183 mg of 70% m-chloroperoxybenzoicacid. Then 10 ml 5% aqueous sodium hydroxide was added to the reactionmixture and the mixed solution was stirred for another 10 minutes. Thedichloromethane was removed in vacuo and the resulting residue wasextracted with 50 ml water and dichloromethane (30 ml×3). The organiclayer was then concentrated under reduced pressure and was purified bycolumn chromatography (hexane/ethylacetate=1:1) to give 310 mg of5-(3-bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone.NMR: δ1.58 (s, 6H), 2.84 (s, 3H), 7.30 (m, 2H), 7.38 (m, 3H), 7.78 (dd,J=8.4, 1.8 Hz, 1H), 7.88 (d, J=5.4 Hz, 1H), 7.90 (d, J=2.7 Hz, 1H). IR(cm⁻¹): 1698, 1619, 1388, 1064.

Compounds of Example 347˜Example 350 were prepared according toprocedures similar to the procedure described for Example 346.

EXAMPLE 347˜EXAMPLE 350

Ex- ample R Melting point & spectral data 347 3-Cl NMR: δ1.58(s, 6H),2.84(s, 3H), 7.15(m, 3H), 7.32(m, 1H), 7.76(dd, J=8.4, 1.8Hz, 1H),7.88(d, J=1.5Hz, 1H), 7.93(d, J=7.8Hz, 1H). IR(cm⁻¹): 1708, 1496, 1417,1386, 1065, 1194, 1080. 348 3-F NMR: δ1.56(s, 6H), 2.85(s, 3H), 7.05(m,3H), 7.34(m, 1H), 7.76(dd, J=8.1, 1.8Hz, 1H), 7.87(d, J=1.8Hz, 1H),7.91(dd, J=8.4Hz, 1H). IR(cm⁻¹): 2981, 1699, 1389, 1261, 1063. 349 2-F,NMR: δ1.59(s, 6H), 2.85(s, 3H), 7.08(m, 3H), 7.74(dd, 5-F J=8.4, 1.5Hz,1H), 7.88(d, J=1.8Hz, 1H), 7.93(d, J= 8.4Hz, 1H). IR(cm⁻¹)1708, 1496,1417, 1386, 1065. 350 3-F, mp: 177-179°C. NMR: δ1.56(s, 6H), 2.86(s,3H), 6.82 5-F (m, 3H), 7.78(m, 1H), 7.82(s, 1H), 7.92(d, J=8.4Hz, 1H).IR(cm⁻¹): 1702, 1626, 1390, 1303, 1120.

EXAMPLE 351

5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

287 mg of5-{3-bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 346) in 40 ml trifluoroacetic anhydride was stirred at 0° C.for an hour. Then the solvent was removed in vacuo, and the resultingresidue was dissolved in 50 ml 1:1 methanol and triethylamine. Thesolution was then stirred at 0° C. for an hour, which was followed byremoval of the solvent in vacuo. The resulting residue was stirred in 30ml dichloromethane, to which was added dropwise 15 ml acetic acidsaturated with chlorine. The reaction solution was stirred at 0° C. for30 minutes. Then acetic acid and the unreacted chlorine were evaporatedoff under reduced pressure. The resulting residue was stirred overnightin 30 ml THF and 5 ml ammonia water. The reaction mixture was thenconcentrated in vacuo and was subjected to extraction with 30 ml waterand dichloromethane (30 ml×3). The organic layer was concentrated invacuo and was purified by column chromatography(hexane/ethylacetate=3:2) to obtain 89 mg of5-{4-(aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 128-132° C. NMR: δ1.63 (s, 6H), 5.32 (br s, 2H), 7.12(m, 2H), 7.40 (m, 3H), 7.69 (m, 1H), 7.98 (m, 2H). IR (cm⁻¹): 3400,3282, 1686, 1556, 1171.

Compounds Example 352 and Example 353 were prepared by proceduressimilar to the procedure for Example 351.

EXAMPLE 352 and EXAMPLE 353

Ex- ample R Melting point & spectral data 352 3-F mp: 151-153°C. NMR:δ1.55(s, 6H), 5.30(br s, 2H), 7.05(m, 3H), 7.36(m, 1H), 7.73(m, 1H),7.92(m, 2H). 353 2-F, NMR: δ1.59(s, 6H), 5.26(br s, 2H), 7.08(m, 3H),7.42 5-F (m, 1H), 7.81(m, 1H), 8.08(m, 1H). IR(cm⁻¹): 3357, 1499, 1335,1171.

EXAMPLE 354

5-{3-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneStep 1: Preparation of1-{3-chloro-4-(methylthio)phenyl}-2-phenyl-ethanone

To a stirred solution of 2-chlorothioanisole (3.0 g) in 120 mldichloromethane, were added slowly first 2.8 g of aluminum chloride and3.0 g of phenylacetyl chloride at 0° C. The reaction mixture was stirredat the temperature for 12 hours. Then the reaction solution was pouredonto ice and aqueous hydrochloric acid. The quenched solution wasstirred for 30 minutes and extracted with dichloromethane (80 ml×3). Theorganic layer was washed with brine and was dried over anhydrousmagnesium sulfate. After the magnesium sulfate was removed byfiltration, the filtrate was concentrated in vacuo. The resultingresidue was recrystallized from hexane and dichloromethane to give 3.6 gof 1-{3-chloro-4-(methylthio)phenyl}-2-phenyl-ethanone. mp: 101-102° C.NMR: δ2.51 (s, 3H), 4.22 (s, 2H), 7.17 (d, J=8.4 Hz, 1H), 7.25 (m, 3H),7.32 (m, 2H), 7.87 (J=8.4, 1.8 Hz, 1H), 7.97 (d, J 1.8 Hz, 1H).

Step 2: Preparation of5-{3-chloro-4-methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

3.6 g of 1-{3-chloro-4-(methylthio)phenyl}-2-phenyl-ethanone in 100 mldry THF was stirred at 0° C. for 20 minutes in the presence of 60% oildispersion of sodium hydride (1.5 g), which was followed by dropwiseaddition of α-bromoisobutyryl cyanide (3.0 ml) diluted in 50 ml THF. Thereaction solution was allowed to warm slowly to room temperature and wasstirred overnight. Then the solvent was removed in vacuo, which wasfollowed by extraction with 30 ml water and diethylether (50 ml×3). Theorganic layer was concentrated under reduced pressure and was purifiedby column chromatography (hexane/ethylacetate=8:1) to yield 3.2 g of5-{3-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone.NMR: δ1.52 (s, 6H), 2.45 (s, 3H), 7.17 (d, J=8.4 Hz, 1H), 7.25 (m, 3H),7.32 (m, 2H), 7.87 (dd, J=8.4, 1.8 Hz, 1H), 7.97 (d, J=1.8 Hz, 1H). IR(cm⁻¹): 1694, 1613, 1592, 1389, 1252, 1145, 1128.

Compounds of Example 355 and Example 356 were prepared by proceduressimilar to the procedures employed for Example 354.

EXAMPLE 355 and Example 356

Ex- ample R Melting point & spectral data 355 3-F NMR: δ1.55(s, 6H),2.49(s, 3H), 7.05(m, 3H), 7.06(d, J= 8.4Hz, 1H), 7.34(m, 1H), 7.44(dd,J=8.4, 1.8Hz, 1H), 7.69(d, J=1.8Hz, 1H). IR(cm⁻¹): 1695, 1616, 1599,1431, 1386, 1257, 1194, 1129. 356 3-F, NMR: δ1.57(s, 6H), 2.51(s, 3H),6.88(m, 3H), 7.09(d, 5-F J=8.4Hz, 1H), 7.44(dd, J=8.4, 1.8Hz, 1H),7.69(d, J= 1.8Hz, 1H). IR(cm⁻¹): 1698, 1623, 1593, 1391, 1309, 1120.

EXAMPLE 357

5-{3-Chloro-4(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

1.2 g of5-{3-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 354) was dissolved in 150 ml of 1:1:1 methanol/THF/water, towhich was added 2.8 g of OXONE. The reaction mixture was stirred at roomtemperature for 6 hours. The reaction mixture was concentrated in vacuoand the resulting residue was extracted with 50 ml water andethylacetate (100 ml×3). The organic layer was concentrated in vacuo andwas purified by column chromatography hexane/ethylacetate=3:1) to give1.1 g of5-{3-chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 174-175° C. NMR: δ1.58 (s, 6H), 3.28 (s, 3H), 7.27 (m,3H), 7.39 (m, 2H), 7.66 (dd, J=8.4, 1.8 Hz, 1H), 7.86 (d, J=1.8 Hz, 1H),8.09 (d, J=8.4 Hz, 1H). IR (cm⁻¹): 1700, 1587, 1391, 1321, 1241, 1152.

Compounds of Example 358˜Example 362 were prepared according to theprocedures similar to the procedure in Example 357.

EXAMPLE 358˜EXAMPLE 362

Ex- ample R Melting point & spectral data 358 3-Cl mp: 188-189°C. NMR:δ1.58(s, 6H), 3.30(s, 3H), 7.14 (m, 1H), 7.34(m, 3H), 7.65(dd, J=8.4,1.8Hz, 1H), 7.87 (d, J=1.5Hz, 1H), 8.12(d, J=8.4Hz, 1H). IR(cm⁻¹): 1700,1620, 1585, 1388, 1321, 1241, 1162. 359 3-F mp: 163-164°C. NMR: δ1.58(s,6H), 3.29(s, 3H), 7.04 (m, 3H), 7.35(m, 1H), 7.66(dd, J=8.4, 1.5Hz, 1H),7.86 (d, 1.5Hz, 1H), 8.12(d, J=8.4Hz, 1H). IR(cm⁻¹): 1701, 1587, 1390,1321, 1262, 1152. MS(FAB): 395(m+1). 360 4-F mp: 173-174°C. NMR:δ1.57(s, 6H), 3.29(s, 3H), 7.11 (m, 2H), 7.26(m, 2H), 7.66(dd, J=8.1,1.5Hz, 1H), 7.85 (d, J=1.8Hz, 1H), 8.12(d, J=8.4Hz, 1H). IR(cm⁻¹): 1698,1587, 1509, 1388, 1321, 1239, 1162. 361 3-F, mp: 150-151°C. NMR:δ1.57(s, 6H), 3.30(s, 3H), 6.99 4-F (m, 1H), 7.17(m, 2H), 7.66(dd,J=8.4, 1.8Hz, 1H), 7.86 (d, J=1.5Hz, 1H), 8.15(d, J=8.4Hz, 1H).IR(cm⁻¹): 1701, 1515, 1393, 1321, 1280, 1152. 362 3-F, mp: 200-201°C.NMR: δ1.58(s, 6H), 3.31(s, 3H), 6.84 5-F (m, 3H), 7.67(dd, J=8.1, 1.5Hz,1H), 7.86(d, J=1.5Hz, 1H), 8.16(d, J=8.1Hz, 1H). IR(cm⁻¹): 1702, 1591,1391, 1320, 1218, 1153, 1120.

EXAMPLE 363

5-{3-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

To a stirred solution 3.5 g of5-{3-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 354) in 80 ml dichloromethane, was added 2.5 g of 70%m-chloroperoxybenzoic acid, and the reaction mixture was stirred at 0°C. for 2 hours. Then 40 ml 5% aqueous sodium bicarbonate was added tothe solution and the solution was stirred for 10 minutes. The solutionwas extracted with dichloromethane (50 ml×3). The organic layer wasconcentrated in vacuo and was purified by column chromatography(hexane/ethylacetate=1:1) to give 2.43 g of5-{3-chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 120-121° C. NMR: δ1.57 (s, 6H), 2.84 (s, 3H), 7.30 (m,3H), 7.38 (m, 2H), 7.72 (s, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.91 (d, J=8.1Hz, 1H). IR (cm⁻¹): 1699, 1619, 1319, 1239, 1169, 1145, 1068.

Compounds of Example 364˜Example 366 were synthesized by employingprocedures similar to the method in Example 363.

EXAMPLE 364˜EXAMPLE 366

Ex- ample R Melting point & spectral data 364 3-Cl mp: 141-142°C. NMR:δ1.57(s, 6H), 2.86(s, 3H), 7.16 (m, 1H), 7.33(m, 3H), 7.72(d, J=1.2Hz,1H), 7.73(dd, J= 8.1, 1.2Hz, 1H), 7.94(d, J=8.1Hz, 1H). IR(cm⁻¹): 1700,1618, 1387, 1239, 1146, 1067. 365 3-F mp: 52-53°C. NMR: δ1.58(s, 6H),2.86(s, 3H), 7.06(m, 3H), 7.35(m, 1H), 7.71(d, J=1.2Hz, 1H), 7.74(dd, J=8.1, 1.5Hz, 1H), 7.94(d, J=7.8Hz, 1H). IR(cm⁻¹): 1701, 1622, 1389, 1309,1147, 1067. 366 3-F, mp: 123-124°C. NMR: δ1.58(s, 6H), 2.88(s, 3H), 6.855-F (m, 3H), 7.71(d, J=1.5Hz, 1H), 7.74(dd, J=8.1, 1.5Hz, 1H), 7.98(d,J=1.8Hz, 1H). IR(cm⁻¹): 1702, 1625, 1591, 1391, 1309, 1119, 1067.

EXAMPLE 367

5-{4-(Aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

1.2 g of5-{3-chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 363) was stirred in 30 ml trifluoroacetic anhydride at 0° C.for 2 hours. Then the solvent was removed under reduced pressure, whichwas followed by addition of 30 ml of 1:1 methanol/triethylamine to theresulting residue. The mixed solution was stirred at 0° C. for an hour,and the solvent was removed in vacuo. The resulting residue wasdissolved, to which was added 30 ml acetic acid saturated with chlorine.The reaction mixture was stirred at 0° C. for 30 minutes. Then thesolvent and the unreacted chlorine were evaporated off under reducedpressure, and the resulting residue was stirred overnight in 30 ml THFand 3 ml ammonia water. The reaction mixture was concentrated in vacuo,and the resulting residue was extracted with 30 ml water anddichloromethane (30 ml×3). The organic layer was washed with brine andthen the organic layer was concentrated under reduced pressure. Theresulting residue was purified by column chromatography(hexane/ethylacetate=3:2) to afford 512 mg of5-{4-(aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 193-194° C. NMR: δ1.58 (s, 6H), 5.14 (br s, 2H), 7.26(m, 3H), 7.39 (m, 2H), 7.62 (dd, J=8.4, 1.8 Hz, 1H), 7.84 (d, J=1.8 Hz,1H), 8.04 (d, J=8.1 Hz, 1H). IR (cm⁻¹): 3379, 3263, 1691, 1586, 1347,1219, 1156.

Compounds of Example 368˜Example 371 were prepared by procedures similarto the procedure adopted for Example 367.

EXAMPLE 368˜EXAMPLE 371

Ex- ample R Melting point & spectral data 368 3-Cl mp: 162-163°C. NMR:δ1.57(s, 6H), 5.18(br s, 2H), 7.13(m, 1H), 7.33(m, 3H), 7.60(dd, J=8.4,1.8Hz, 1H), 7.85(d, J=1.5Hz, 1H), 8.07(d, J=8.4Hz, 1H). IR(cm⁻¹): 3384,3264, 1695, 1617, 1391, 1351, 1241, 1166. 369 3-F mp: 149-150°C. NMR:δ1.57(s, 6H), 5.15(br s, 2H), 7.04(m, 3H), 7.36(m, 1H), 7.61(dd, J=8.4,1.8Hz, 1H), 7.83(d, J=1.5Hz, 1H), 8.07(d, J=8.4Hz, 1H). IR(cm⁻¹): 3377,3265, 1692, 1587, 1393, 1349, 1261, 1165. 370 3-F, mp: 216-217°C. NMR:δ1.57(s, 6H), 5.18(br s, 2H), 4-F 6.99(m, 1H), 7.17(m, 2H), 7.61(dd,J=8.4, 1.8, 1H), 7.84(d, J=1.5Hz, 1H), 8.10(d, J=8.1Hz, 1H). IR(cm⁻¹):3401, 3264, 1687, 1515, 1396, 1220, 1165. 371 3-F, mp: 173-174°C. NMR:δ1.58(s, 6H), 5.19(br s, 2H), 5-F 6.84(m, 3H), 7.61(dd, J=8.4, 1.8Hz,1H), 7.84(d, J= 1.8Hz, 1H), 8.11(d, J=8.1Hz, 1H). IR(cm⁻¹): 3370, 3265,1692, 1625, 1393, 1309, 1165, 1119.

EXAMPLE 372

5-{3-Chloro-4-(N-methylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

200 mg of2,2-dimethyl-5-{3-chloro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone(Example 363) was stirred in 10 ml trifluoroacetic anhydride for an hourat 0° C. and then the solvent was removed in vacuo. The resultingresidue was dissolved in 10 ml 1:1 methanol/triethylamine and wasstirred for an hour at 0° C. The solution was concentrated under reducedpressure. Then the resulting residue was stirred in 15 mldichloromethane, to which was added 5 ml acetic acid saturated withchlorine. After the solution was stirred for 30 minutes at 0° C., thesolvent and the unreacted chlorine were removed in vacuo. The resultingresidue was dissolved in 5 ml toluene and the toluene was evaporated offin vacuo. The resulting residue was dissolved in 20 ml THF and reactedwith 1 ml of 40% aqueous methylamine for 2 hours at 0° C. The reactionsolution was concentrated in vacuo, which was followed by extractionwith 30 ml water and dichloromethane (30 ml×3). The organic layer waswashed with brine and concentrated under reduce pressure. The resultingresidue was purified by column chromatography (hexane/ethylacetate=3:2)to give 62 mg of5-{3-chloro-4-(N-methylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 136-137° C. NMR: δ1.58 (s, 6H), 2.66 (d, J=5.4 Hz, 3H),4.94 (q, J=5.4 Hz, 1H), 7.28 (m, 2H), 7.39 (m, 3H), 7.63 (dd, J=8.4, 1.8Hz, 1H), 7.84 (d, J=1.8 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H). IR (cm⁻¹):3315, 1697, 1587, 1394, 1336, 1242, 1164.

EXAMPLE 373

5-{3-Chloro-4-(N-ethylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

By following the procedure in Example 372 except using 70% aqueousethylamine, the titled compound was obtained. mp: 72-73° C. NMR: δ1.11(t, J=7.2 Hz, 3H), 1.57 (s, 6H), 3.02 (m, 2H), 4.93 (t, J=6.0 Hz, 1H),7.28 (m, 2H), 7.39 (m, 3H), 7.62 (dd, J=8.4, 1.8 Hz, 1H), 7.83 (d, J=1.8Hz, 1H), 8.03 (d, J=8.1 Hz, 1H). IR (cm⁻¹):3300, 1698, 1618, 1587, 1393,1337, 1241, 1163.

EXAMPLE 374

5-[4{(Acetylamino)sulfonyl}-3-chlorophenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone

150 mg of5-{4-(aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2furanone(Example 367) in 10 ml dichloromethane was reacted with 0.3 ml aceticanhydride in the presence of 0.5 ml triethylamine and 15 mg of4-(N,N-dimethylamino)pyridine at room temperature for 12 hours. Thereaction mixture was concentrated in vacuo, which was followed byextraction with 30 ml water and dichloromethane (30 ml×3). The organiclayer was concentrated under reduced pressure and then was purified bycolumn chromatography (hexane/ethylacetate 2:1) to afford 113 mg of5-[4-{(acetylamino)sulfonyl}-3-chlorophenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 194-195° C. NMR: δ1.57 (s, 6H), 2.10 (s, 3H), 7.27 (m,2H), 7.40 (m, 3H), 7.68 (dd, J=8.4, 1.8 Hz, 1H), 7.85 (d, J=1.5 Hz, 1H),8.18 (d, J=8.1 Hz, 1H), 8.45 (br s, 1H). IR (cm⁻¹): 3195, 3104, 1698,1377, 1164.

EXAMPLE 375

5-[3-Chloro-4-{(propionylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone

150 mg of5-{4-(aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 367) was reacted with propionic anhydride to give 132 mg of5-[3chloro-4-{(propionylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanoneaccording to a procedure similar to the procedure of Example 374. mp:191-192° C. NMR: δ1.09 (t, J=7.5 Hz, 3H), 1.57 (s, 6H), 2.32 (q=7.5 Hz,2H), 7.27 (m, 2H), 7.39 (m, 3H), 7.68 (dd, J=8.4, 1.8 Hz, 1H), 7.84 (d,J=1.5 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.37 (br s, 1H). IR (cm⁻¹): 3204,3105, 1699, 1458, 1396, 1164.

EXAMPLE 376

5-[4-{(n-Butyrylamino)sulfonyl}-3-chlorophenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone

150 mg of5-{4-(aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 367) was reacted with butyric anhydride to give 124 mg of5-[3-chloro-4-{(n-butrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanoneaccording to a procedure similar to the procedure of Example 374. mp:119-120° C. NMR: δ0.89 (t, J=7.5 Hz, 3H), 1.57 (s, 6H), 1.59 (m, 2H),2.27 (t, J=7.5 Hz, 2H), 7.28 (m, 2H), 7.40 (m, 3H), 7.69 (dd, J=8.4, 1.8Hz, 1H), 7.83 (d, J=1.8 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.48 (br s,1H). IR (cm⁻¹): 3191, 3105, 1698, 1684, 1453, 1242, 1187.

EXAMPLE 377

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone.

437 mg of 1-{3-methyl-4-(methylthio)phenyl}-2-(3-fluorophenyl)-ethanonein 50 ml dry THF was stirred with 67 mg of 60% oil dispersion of sodiumhydride for an hour at 0° C., which was followed by dropwise addition of0.8 ml α-bromoisobutyryl cyanide diluted with 25 ml THF. The reactionsolution was slowly warmed to room temperature and was stirredovernight. Then the solvent was removed in vacuo and the resultingresidue was extracted with 50 ml water and dichloromethane (50 ml×3).The organic layer was concentrated in vacuo and was purified by columnchromatography (hexane/ethylacetate=6:1) to yield 312 mg of2,2-dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone.NMR: δ1.55 (s, 6H), 2.27 (s, 3H), 2.48 (s, 3H), 7.36 (m, 4H), 7.32 (m,1H), 7.45 (m, 2H). IR 1694, 1601, 1385, 1260, 1192.

EXAMPLE 378

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone

257 mg of2,2-dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylthio)-phenyl}-3(2H)-furanone(Example 377) in 50 ml methylenechloride was stirred with 170 mg of 70%m-chloroperoxybenzoic acid at 0° C. for an hour, which was followed byaddition of 10 ml 5% aqueous sodium bicarbonate. Then the solution wasstirred for another 10 minutes. The reaction mixture was concentrated invacuo and was extracted with 50 ml water and dichloromethane (30 ml×3).The organic layer was concentrated under reduced pressure and waspurified by column chromatography (hexane/ethylacetate 2:1) to afford 43mg of2,2-dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanoneas a solid. mp: 138-139° C. NMR: δ1.57 (s, 6H), 2.68 (s, 3H), 3.09 (s,3H), 7.03 (m, 3H), 7.28 (m, 1H), 7.58 (dd, J=8.4, 1.8 Hz, 1H), 7.63 (d,J=1.2 Hz, 1H), 8.01 (d, J=8.4 Hz, 1H). IR (cm⁻¹): 1698, 1589, 1387,1312, 1262. MS (FAB): 374 (m+1).

EXAMPLE 379

2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone

219 mg of2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfinyl)-phenyl}-3(2H)-furanonewas obtained as a co-product during the synthesis of Example 378. NMR:δ1.56 (s, 6H), 2.32 (s, 3H), 2.70 (s, 3H), 7.04 (m, 3H), 7.31 (m, 1H),7.49 (d, J=0.9, 1H), 7.67 (dd, J=8.1, 1.8 Hz, 1H), 7.94 (d, J=8.4, 1H).IR (cm⁻¹): 1697, 1384, 1259, 1204, 1072.

EXAMPLE 380

5-{4-(Aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone

201 mg of2,2-dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfinyl)-phenyl}-3(2H)-furanone(Example 379) was converted into 76 mg of5-{4-(aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanoneby following a procedure similar to the procedure used in Example 367.mp: 81-82° C. NMR: δ1.57 (s, 6H), 2.63 (s, 3H), 5.13 (br s, 2H), 7.03(s, 3H), 7.27 (m, 1H), 7.45 (m, 1H), 7.61 (m, 1H), 7.96 (d, J=8.4 Hz,1H). IR (cm⁻¹): 3369, 3270, 1589, 1334, 1168. MS (FAB): 375 (m+1).

EXAMPLE 381

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone

530 mg of1-{3-methyl-4-(methylthio)phenyl}-2-(3,5-difluorophenyl)-ethanone wasconverted into 357 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanoneby following a procedure similar to the procedure of Example 377. NMR:δ1.55 (s, 6H), 2.29 (s, 3H), 2.50 (s, 3H), 6.74 (m, 1H), 6.89 (m, 2H),7.08 (d, J=8.1 Hz, 1H), 7.40 (dd, J=8.4, 2.1 Hz, 1H), 7.45 (d, J=1.5 Hz,1H). IR (cm⁻¹): 1691, 1601, 1384, 1910, 1118.

EXAMPLE 382

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone

105 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)-phenyl}-3(2H)-furanone(Example 381) was dissolved in 50 ml methanol, 30 ml THF and 50 mlwater, to which was added 513 mg of OXONE. The reaction mixture wasstirred at room temperature for 4 hours. Then the mixture wasconcentrated in vacuo, and was extracted with water 50 ml anddichloromethane (30 ml×3). Concentration of the organic layer underreduced pressure was followed by column chromatography(hexane/ethylacetate=3:2) to give 97 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone.NMR: δ1.57 (s, 6H), 2.71 (s, 3H), 3.05 (s, 3H), 6.82 (m, 1H), 7.12 (m,1H), 7.59 (m, 1H), 7.63 (m, 1H), 7.92 (m, 2H).

EXAMPLE 383

4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone

To 320 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone(Example 381) in 50 ml dichloromethane, was added 172 mg of 70%m-chloroperoxybenzoic acid. The mixture was stirred at 0° C. for anhour, which was followed by addition of 30 ml 5% aqueous sodiumbicarbonate. The solution was stirred for another 10 minutes. Then themixture was concentrated in vacuo, and was extracted with 50 ml waterand dichloromethane (30 ml×3). Then the organic layer was concentratedunder reduced pressure and was purified by column chromatography(hexane/ethylacetate=1:1) to give 211 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone.NMR: δ1.57 (s, 6H), 2.36 (s, 3H), 2.73 (s, 3H), 6.77 (m, 1H), 6.86 (m,2H), 7.50 (m, 1H), 7.66 (m, 1H), 7.99 (d, J=8.4 Hz, 1H). IR (cm⁻¹):1698,1624,1592,1384, 1310,1206,1072,915.

EXAMPLE 384

5-{4-(Aminosulfonyl)-3-methylphenyl}-4-(3-difluorophenyl)-2,2-dimethyl-3(2H)-furanone

240 mg of4-(3,5-difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methyl-sulfinyl)phenyl}-3(2H)-furanonewas converted into 33 mg of5-{4-(aminosulfonyl)-3-methylphenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanoneby a procedure similar to the procedure used for Example 367. NMR: δ1.56(s, 6H), 2.66 (s, 3H), 4.98 (br s, 2H), 6.85 (m, 3H), 7.41 (m, 1H), 7.80(m, 1H), 7.92 (m, 1H).

EXAMPLE 385

4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione

130 mg of4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)-phenyl}-3(2H)-furan-3-thione(Example 278) in 20 ml toluene was stirred at reflux for 12 hours in thepresence of 67 mg of Lawesson's reagent. Then the solvent was removed invacuo and the resulting residue was extracted with 50 ml water anddichloromethane (50 ml×3). The organic layer was concentrated underreduced pressure and was purified by column chromatography(hexane/ethylacetate=4:1) to give 117 mg of4-(3-chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-(2H)-furan-3-thioneas a solid. mp: 105-106° C. NMR: δ1.71 (s, 6H), 3.24 (s, 3H), 7.12 (m,3H), 7.41 (m, 1H), 7.52 (m, 2H), 7.92 (dd, J=7.8, 7.2 Hz, 1H). IR(cm⁻¹): 1604, 1557, 1324, 1273, 1209, 1145, 1047, 963.

EXAMPLE 386

5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-(2H)-furan-3-thione

140 mg of5-{(aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone(Example 312) was converted into 103 mg of5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(3,5-difluorophenyl)-(2H)-furan-3-thioneby a procedure similar to the procedure employed for Example 385. mp:153-154° C. NMR: δ1.71 (s, 6H), 5.12 (br s, 2H), 6.84 (m, 3H), 7.48 (m,2H), 7.90 (dd, J=8.1, 8.1 Hz, 1H). IR (cm⁻¹): 3416, 3279, 1624, 1557,1356, 1273, 1173, 1121, 1064.

EXAMPLE 387

5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

3.05 g of 1-{2-chloro-4-(methylthio)phenyl}-2-phenyl-ethanone in 60 mldry THF was stirred at 0° C. for 20 minutes in the presence of 95% oildispersion of sodium hydride (1.0 g), which was followed by dropwiseaddition of α-bromoisobutyryl cyanide (2.5 ml) diluted in 50 ml THF. Thereaction solution was allowed to warm slowly to room temperature and wasstirred overnight. Then the solvent was removed in vacuo, which wasfollowed by extraction with 30 ml water and diethylether (50 ml×3). Theorganic layer was concentrated under reduced pressure and was purifiedby column chromatography (hexane/ethylacetate=8:1) to yield 2.73 g of5-{2-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone.NMR: δ1.56 (s, 6H), 2.48 (s, 3H), 7.10 (dd, J=8.4, 1.5 Hz, 1H), 7.24 (m,3H), 7.26 (m, 3H), 7.37 (d, J=1.5 Hz, 1H). IR (cm⁻¹): 1698, 1620, 1394,1235, 1176, 1144.

Compound of Example 388 was prepared by procedures similar to theprocedures employed for Example 387.

EXAMPLE 388

Ex- ample R Melting point & spectral data 388 3-F NMR: δ1.56(s, 6H),2.51(s, 3H), 6.89(m, 1H), 7.01(m, 2H), 7.14(dd, J=8.4, 1.8Hz, 1H),7.19(m, 1H), 7.26(d, J= 3.3Hz, 1H), 7.28(d, J=1.8Hz, 1H). IR(cm⁻¹):2981, 1701, 1615, 1376, 1200.

EXAMPLE 389

5-{2-Chloro-4(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

350 mg of5-{2-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 387) was dissolved in 75 ml of 1:1:1 methanol/THF/water, towhich was added 1.0 g of OXONE. The reaction mixture was stirred at roomtemperature for 6 hours. The reaction mixture was concentrated in vacuoand the resulting residue was extracted with 25 ml water andethylacetate (50 ml×3). The organic layer was concentrated in vacuo andwas purified by column chromatography (hexane/ethylacetate=3:1) to give252 mg of5-{2-chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 89-90° C. NMR: δ1.59 (s, 6H), 3.11 (s, 3H), 7.19 (m,2H), 7.25 (m, 3H), 7.60 (d, J=8.1 Hz, 1H), 7.87 (dd, J=8.1, 1.8 Hz, 1H),8.07 (d, J=1.8 Hz, 1H). IR (cm⁻¹): 1701, 1625, 1586, 1391, 1319, 1153.

Compound of Example 390 was prepared according to procedures similar tothe procedure in Example 389.

EXAMPLE 390

Ex- ample R Melting point & spectral data 390 3-F mp: 97-98°C. NMR:δ1.59(s, 6H), 3.12(s, 3H), 6.88- 7.02(m, 3H), 7.21(m, 1H), 7.62(d,J=7.8Hz, 1H), 7.91(dd, J=7.8, 1.8Hz, 1H), 8.08(d, J=1.8Hz, 1H).IR(cm⁻¹): 1702, 1626, 1392, 1319, 1262, 1154.

EXAMPLE 391

5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone

To a stirred solution 2.7 g of5-{2-chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone(Example 387) in 80 ml dichloromethane, was added 1.94 g of 70%m-chloroperoxybenzoic acid. The reaction mixture was stirred at 0° C.for 2 hours. Then 40 ml 5% aqueous sodium bicarbonate was added to thesolution and the solution was stirred for 10 minutes. The solution wasextracted with dichloromethane (50 ml×3). The organic layer wasconcentrated in vacuo and was purified by column chromatography(hexane/ethylacetate=1:1) to give 978 mg of5-{2-chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanoneas a solid. mp: 135-136° C. NMR: δ1.59 (s, 6H), 2.78 (s, 3H), 7.22 (m,3H), 7.25 (m, 2H), 7.54 (m, 2H), 7.79 (m, 1H). IR (cm⁻¹): 1698, 1623,1392, 1242, 1145, 1063.

Compound of Example 392 was synthesized by employing procedures similarto the method for Example 391.

EXAMPLE 392

Example R Melting point & spectral data 392 3-F Mp: 109-110° C. NMR: δ1.59(s, 6H), 2.79(s, 3H), 6.91-7.01(m, 3H), 7.20(m, 1H), 7.57(m, 2H),7.80(m, 1H). IR (cm⁻¹): 1701, 1623, 1582, 1392, 1261, 1194, 1062.

EXAMPLE 393

4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone

To a stirred solution of 10.98 g of4-(3-chlorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone(Example 168) in 250 ml of dichloromethane was added dropwise 6.59 g of70% m-chloroperoxybenzoic acid dissolved in 150 ml of dichloromethane.The reaction mixture was stirred for 1 hr at 0° C. The reaction mixturewas purified following by procedure of Step 1 of Example 22 to give 6.33g of4-(3-chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl})-3(2H)-furanone.mp: 109-110° C. NMR: δ1.57 (s, 6H), 2.75 (s, 3H), 7.17 (m, 1H), 7.31 (m,2H) 7.65 (d, J=8.4 Hz, 2H), 7.80 (d, J=8.7 Hz, 2H).

BIOLOGICAL EVALUATION

Evaluation of in vitro COX-2 and COX-1 Activity [J. Pharmacol. Exp.Ther. 166, 96 (1969)]

Harvest of Mouse Peritoneal Macrophages

The abdominal skin of a C57BL/6 mouse was sanitized with 70% aqueousethanol, and was removed without damaging the peritoneum. 5 ml of coldphosphate buffer solution (PBS) was then injected into the abdominalcavity. After a minute, the peritoneal fluid containing the macrophageswas collected using a syringe and a needle. The collected fluid wascentrifuged for 5 min at 1500 rpm to afford pellets of cells. Thepellets were then dispersed in the RPMI-1640 culture medium containing100 units/ml penicillin and 100 μg/ml streptomycin.

Evaluation of COX-2 Activity

The pellets dispersed as above were treated with 500 μM aspirin in orderto knock out the activity of the COX-1 enzymes in the cells. Thesuspension was then diluted with the RPMI-1640 medium to contain 1×10⁶cells/ml. 100 μl of the suspension was added to each well of a 96-wellELISA plate. Then the plate was incubated for 2 hrs at 37° C. under 5%CO₂ in order to fix the macrophages onto the plate. The cells, whichwere not fixed onto the plate were removed by washing with PBS twotimes. The purity of macrophages obtained thereby was confirmed bydifferential counting. The RPMI-1640 medium containing 3% fetal bovineserum albumin was added to each well of the plate, which was followed bystimulation with 10 μg/ml lipopolysaccharide (LPS). Usually 5×10⁵cells/ml were present by this preparation. The LPS-treated suspensionswere incubated for 16 hours at 37° C. under 5% CO₂ to induce COX-2. Thenthe culture medium was removed and the macrophages were washed two timeswith PBS. Then 130 μl RPMI-1640 culture medium was added to each welland the macrophage solutions were incubated at 37° C. for 10 minutes,which was followed by the treatment with 10 μM arachidonic acid and anappropriate amount of compounds of this invention. The plate wasincubated for another 10 minutes. The upper solution was collected usinga micropipette and was subjected to determination of PGE₂ amount in thesolution. The amount of PGE₂ present in the collected solution wasdetermined either by a known radio-immuno assay or by a knownenzyme-immunoassay [Methods in Enzymol. 86, 258 (1982); Methods inEnzymol. 187, 24 (1990)]. The extent of COX-2 inhibition by a compoundof the present invention was calculated by assuming, that the amount ofPGE₂ formed with the treatment of 10 μg/ml arachidonic acid was used isthe maximum possible amount of PGE₂, and that the amount of PGE₂ formedwithout the treatment of arachidonic acid is the minimum possible amountof PGE₂.

Evaluation of COX-1 Activity

In the evaluation of COX-1 inhibitory activity by a compound of thepresent invention, the same procedures employed for evaluation of COX-2activity were employed, except omitting the following two steps: 1) thetreatment with aspirin for knockout of COX-1 activity and 2) treatmentwith LPS for induction of COX-2.

IC₅₀ data of COX-1 and COX-2 for selected compounds of the presentinvention were summarized in the following Table 1. IC₅₀ denotes aconcentration of a compound, at which the enzymatic activity of COX-1 orCOX-2 reaches 50% of the activity in the absence of compound treatment.In order to determine IC₅₀ for a compound of this invention, enzymaticactivities were measured at multiple concentrations of compounds of thisinvention around IC₅₀ of the compound. Usually enzymatic activities at4˜5 concentrations were measured to calculate out IC₅₀ for a compound ofthis invention.

TABLE 1 in vitro Activities of COX-2 inhibitors. IC₅₀, μg/ml IC₅₀, μg/mlExample COX-2 COX-1 Example COX-2 COX-1  4 0.02 5 214 0.03 3  5 0.05 50216 0.03 20  6 0.05 5 225 0.03 3  10 0.3 50 236 0.0097 10.7  11 0.05 20245 0.03 3  17 0.2 30 246 0.03 3  18 0.2 30 254 0.03 3  24 0.034 6.97255 0.03 3  25 0.013 3.46 256 0.03 5  31 0.2 20 261 1 300  36 0.2 50 2630.03 50  44 0.101 >10 273 0.03 20  45 0.01 1.07 275 0.03 200  49 0.3 30276 0.05 10  50 0.03 20 278 0.05 30  53 0.03 5 281 0.1 10  54 0.05 10282 0.03 30  62 0.01 2 283 0.7 90  64 0.1 50 284 0.03 10  66 0.05 50 2850.03 200  69 0.3 50 286 0.03 5  75 0.03 3 290 0.3 20  76 0.5 50 291 0.23  77 0.003 5 300 0.03 20  80 0.05 5 302 0.03 5  84 0.03 3 303 0.03 3 86 0.03 30 304 0.05 50  94 0.05 5 305 0.003 0.3  95 0.1 30 311 0.03 3 96 0.02 3 312 0.02 100  97 0.002 5 321 0.03 20 103 0.03 20 322 0.02 3104 0.3 100 323 0.03 10 105 0.03 50 324 0.03 3 111 0.3 50 325 0.05 200113 0.03 3 326 0.03 20 121 0.2 30 332 0.03 5 122 0.03 3 333 0.003 10 1230.3 50 334 0.03 3 126 0.014 3.82 335 0.003 3 127 0.001 0.12 340 10 30129 0.0067 1.02 341 0.3 90 132 0.0178 7.42 342 0.02 30 135 0.055 >10 3430.03 50 138 0.0067 1.94 344 0.08 200 146 0.0014 0.83 345 0.03 50 1490.0087 1.01 351 0.9 300 151 0.0188 >10 357 0.05 30 155 0.016 1.8 3580.02 8 157 0.038 5.15 359 0.02 200 160 0.057 >10 360 0.009 3 164 0.03100 361 0.009 4 167 3 50 362 0.05 300 168 0.5 3 367 0.06 8 175 3 30 3680.02 7 176 1 10 369 0.02 50 177 5 30 371 0.02 200 188 0.3 30 372 0.09200 193 0.03 3 373 0.3 600 194 0.05 20 378 0.03 3 195 0.03 5 382 0.08200 198 0.03 3 384 0.08 30 200 0.3 30 385 0.03 0.05 201 0.1 20 393 0.3 5202 0.03 3

Evaluation of in vivo Antiinflammatary Potency

Carrageenan-induced Foot Edema in Rats (CFF)

An appropriate amount of a compound of this invention suspended in 1%methylcellulose (MC) solution was administered to male Sprague-Dawley(SD) rats weighing 150˜200 g by oral gavage. The volume of theadministered vehicle for a compound of this invention was controlled tobe smaller than 10 ml/kg body weight of the animal. One hour later, 0.1ml of 1% Carrageenan saline solution was directly injected into theright paw of the rats to induce edema in the paw. The paw volumes at 0hour and at 3 hours after the injection of Carrageenan were measured byusing a displacement plethysmometer (Ugo Basile, Italy). The paw volumeswere used to calculate % inhibition of CFE by an amount of a compound ofthis invention according to the following equation. [Br. J. Pharmacol.41, 132 (1971)]

% Inhibition of CFE=(1−Δtreated/Δcontrol)×100

wherein Δtreated=[paw volume at three hours after the Carrageenaninjection−paw volume right after Carrageenan injection] for adrug-administered rat, and Δcontrol=[paw volume at three hours after theCarrageenan injection−paw volume right after Carrageenan injection] fora rat without drug administration.

CFE inhibition data for selected compounds of this invention aresummarized in the following Table 2. In order to determine theinhibitory activity of a compound of this invention at a dose, usually 5to 8 animals were used both for drug-treated group and for controlgroup.

TABLE 2 in vivo Antiinflammatory potency of COX-2 inhibitors (CFE) Dose(oral), Example % Inhibition mg/kg body weight Indomethacin 28 1  4 36 3 14 32 3  20 36 3  23 33 3  84 25 3 126 39 3 129 47 3 146 24 3 155 35 3157 41 3 164 29 3 176 23 3 177 37 3 195 28 3 255 31 3 276 26 3 278 27 3284 33 3 302 27 3 303 30 3 308 32 3 311 30 3 312 31 3 333 25 3 334 37 3335 32 3 343 25 3 359 28 3 361 41 3 369 28 3

Evaluation of Antiinflammatory Potency by Adjuvant Arthritis

Arthritis was induced in male SD rats weighing 180-200 g by subcutaneousinjection of Mycobacterium butyricum mixed in 0.1 ml of incompleteFreund's adjuvanat into the base of the tail. The foot volumes weremeasured using a displacement plethysomometer 14 days after theinjection of the adjuvant. Animals with paw volumes greater than thenormal paw volumes (without the adjuvant treatment) by 0.37 ml wereselected, and then randomized. A designated daily dose of a compound ofthis invention, which was suspended in 1% aqueous methylcellulosesolution, was administered to the randomized rats with arthritis by oralgavage daily once beginning on day 14 after the injection of theadjuvant. The administration of the compound continued till day 22 afterthe injection of the adjuvant, and the paw volumes were measured ondaily basis using a displacement plethysmometer. The paw volumes of 5 to8 rats on day 22 were averaged to determine % inhibition of adjuvantarthritis (AA) by a compound of this invention according to thefollowing equation.

% Inhibition of AA=(1−Δtreated/Δcontrol)×100

wherein Δtreated=[(paw volume at day 22)/(paw volume at day 14)−1] for adrug-administered rat, and Δcontrol=[(paw volume at day 22)/(paw volumeat day 14)−1] for a rat without drug administration.

Ed₅₀ data for adjuvant arthritis for selected compounds of thisinvention were summarized in the following Table 3. ED₅₀ for adjuvantdenotes a daily dose of a compound, at which 50% inhibition of adjuvantarthritis is achieved. ED₅₀ value was determined b a dose-response curvefor each compound.

TABLE 3 in vivo Antiinflammatory potency of COX-2 inhibitors (AA)Adjuvant Arthritis ED₅₀, Example mg/kg body weight  4 0.07  11 0.03  140.06 126 0.03 129 0.02 334 0.09

Pharmacokinetic Studies in Rats

An appropriate amount of a compound suspended 1% aqueous methylcellulosesolution was administered to a male SD rat by oral gavage. Blood sampleswere collected from the retro-orbital sinus at designated times over24˜48 hours. Plasma was separated from each blood sample bycentrifugation and the plasma was stored at 4° C. until analysis. Theplasma samples prepared thereby were subjected to analysis by reversephase HPLC (high performance liquid chromatography) using an appropriateinternal standard.

FIG. 1 shows a pharmacokinetic study for Example 393 orally administeredto a SD rat. Detection of appreciable amounts of Example 62 in theplasma clearly indicates that the sulfoxide group of Example 393 isbiotransformed into the sulfonyl group.

Sulfoxide compounds of this invention are inhibitors of COX-2themselves, however, they can be transformed into the correspondingsulfones after absorption into the body as exemplified by thepharmacokinetic study for Example 393 (FIG. 1). Thus, a sulfoxidecompound of this invention can be used as a prodrug for thecorresponding sulfone.

Analgesic Studies

Acetic Acid-induced Writhing Test

ICR mice weighing 18˜22 g were maintained in a controlled lightingenvironment (12 hours on/12 hours off) and fasted overnight prioranalgesic testing. Mice were administered with a compound of thisinvention dissolved in 10:10:80 ethanol/Tween 80/saline or vehicle onlyby oral gavage. The administered vehicle volume was controlled to be 10ml/kg body weight. One hour later, the animals were treated with 0.2 mlof 1.2% acetic acid by peritoneal injection. 6 minutes later, the numberof abdominal constrictions was counted for a 6 minutes period. Theantinociceptive activity was expressed as the reduction in the number ofabdominal constrictions, compared with that of the placebo group [J.Med. Chem. 39, 4942 (1996)]. ED₅₀ of the mouse writhing test denotes adose level at which the number of abdominal constrictions is half thatof the placebo group. Ten animals per group were used for this study.

Carrageenan-induced Thermal Hyperalgesia Assay

Male SD rats weighing 170˜220 g were fasted but with free access towater for at leat 16 hours prior to testing. The rats were administeredwith a compound of this invention suspended in 20 ml 0.5%methylcellulose/0.025% Tween-20, or with vehicle only. Then the ratswere given 100 ml of 1% carrageenan in saline or 100 ml saline only intothe plantar surface of the left hindpaw by injection. Three hours later,the nociceptive responses to thermal stimuli were assessed as follows:Rats, which were placed in a transparent plastic chamber with a glassfloor, were allowed to acclimate to their environment for 10 minutesprior to the testing. The withdrawal latency period in seconds wasdetermined for the control and the compound treated group, and a percentinhibition in the withdrawal latency was calculated to estimate theanalgesic effect of the compound [Pain 32, 77 (1988)]. In this study 6animals were used for each group.

Analgesic potency for two of compounds of this invention are presentedin the following Table 4 along with that of indomethacin for comparison.

TABLE 4 Analgesic potency of COX-2 inhibitor % Inhibition ED₅₀, mg/kgbody weight at 1.0 mg/kg body weight Compound (mouse writhing) (rathyperalgesia) Example 4 8.3 27% Example 129 12.3 92% Indomethacin 7.445%

Gastric Safety Studies

Gastric safety for compounds of this invention was evaluated as follows[Otterness et al., Laboratory Models for Testing NonsteroidalAnti-inflammatory Drugs in Nonsteroidal Anti-inflammatory Drugs; ed JohnWiley & Sons pp 217-227 (1985); Wiley Interscience; New York]: Adesignated dose of a compound of this invention suspended in 1%methylcellulose solution was administered daily once for 7 days to amale SD rat by oral gavage. The animal was sacrificed and the inner wallof the stomach was examined visually 4 hours after the lastadministration (the 7th day administration). The gastric safety wasassessed by the “Ulcer Index” as defined as the following scores:

Score 1: apparently normal stomach.

Score 2: one or more than one ulcer site of pin-point size only.

Score 3: erosions of 2 or fewer than 2, which may be accompanied byulcers of pin-point size (an erosion is defied by any ulcerative lesionof any dimension greater than 1 mm).

Score 4: erosions more than 2, which may be accompanied by ulcers ofpin-point size.

Score 5: erosions accompanied by hemorrhage.

In evaluating the gastric safety of a compound of this invention,usually 8 animals were used. The ulcer index for a compound wascalculated by averaging of the ulcer index of each animal. The followingTable 5 illustrates gastric safety of some COX-2 selective inhibitors ofthis invention.

TABLE 5 Gastric safety of COX-2 inhibitors Group Daily Dose, mg/kg bodyweight Ulcer Index (1˜5) Placebo — 1.8 ± 1.0 Example 4 30 1.8 ± 0.7Example 10 30 1.2 ± 0.4 Example 11 30 1.8 ± 1.0

The above described discussion of this invention is directed primarilyto preferred embodiments and practices thereof. It will be readilyapparent to those skilled in the art that further changes andmodifications in the actual implementation of the concepts describedherein can readily be made without departing from the spirit and scopeof the invention as defined by the following claims.

What is claimed is:
 1. A compound of the following Formula I:

wherein X represents halo, hydrido, or alkyl; Y representsalkylsulfonyl, aminosulfonyl, alkylsulfinyl, (N-acylamino)-sulfonyl,(N-alkylamino)sulfonyl, or alkylthio; Z represents oxygen or sulfuratom; R₁ and R₂ are selected independently from lower alkyl radicals;and AR represents a substituted or non-substituted aromatic group of 5to 10 atoms; or a pharmaceutically-acceptable salt thereof.
 2. Acompound according to claim 1, wherein X is selected from halo, hydridoand lower alkyl; Y is selected from (lower alkyl)sulfonyl,aminosulfonyl, (lower alkyl)sulfinyl, (lower N-acylamino)-sulfonyl,(lower N-alkylamino)sulfonyl and (lower alkyl)thio; Z is selected fromoxygen and sulfur atom; wherein R₁ and R₂ are selected independentlyfrom lower alkyl radicals; and AR represents a substituted ornon-substituted aromatic group of 5 to 10 atoms, which is selected fromthe group consisting of

wherein, each of R₃ to R₇, if present, is independently selected fromthe group consisting of hydrido, halo, alkyl, haloalkyl, alkoxy,haloalkoxy, acyl, nitro, amino, N-alkylamino, N,N-dialkylamino,N-acylamino, (haloacyl)amino, formyl, cyano, azido, hydroxy, alkylthio,alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or the adjacent twogroups of R₃ to R₇ form, taken together, methylenedioxy; and whereineach of R₈ to R₁₉, if present, is selected from the group consisting ofhydrido, halo, alkyl, acyl, haloalkyl, alkoxy, formyl, cyano, nitro,amino, azido and N-acylamino; or a pharmaceutically-acceptable saltthereof.
 3. A compound according to claim 1 or 2, in which X is selectedfrom fluoro, chloro, bromo, hydrido, methyl, ethyl and n-propyl; Y isselected from methylsulfonyl, ethylsulfonyl, n-propylsulfonyl,aminosulfonyl, methylsulfinyl, ethylsulfinyl, n-propylsulfinyl,(N-acetylamino)sulfonyl, (N-propionylamino)sulfonyl,(N-butyrylamino)sulfonyl, (N-methylamino)sulfonyl,(N-ethylamino)sulfonyl, methylthio, ethylthio, and n-propylthio; Z isselected from oxygen and sulfur atom; wherein R₁ and R₂ are selectedindependently from methyl and ethyl; each of R₃ to R₇, if present, isindependently selected from the group consisting of hydrido, fluoro,chloro, bromo, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,t-butyl, n-pentyl, iso-pentyl, fluoromethyl, difluoromethyl,trifluoromethyl, 2-fluoroethyl, 1-fluoroethyl, 2,2-difluoroethyl,1,2-difluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, methoxy,ethoxy, n-propyloxy, iso-propyloxy, n-butoxy, trifluoromethoxy,difluoromethoxy, fluoromethoxy, acetyl, propionyl, n-butanoyl,iso-butanoyl, n-pentanoyl, nitro, amino, N-methylamino, N-ethylamino,N-n-propylamino, N,N-dimethylamino, N-acetylamino, N-propionylamino,N-(trifluoroacetyl)amino, formyl, hydroxy, methylthio, ethylthio,n-propylthio, methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, phenyl,hydroxymethyl, 1-hydroxyethyl and 2-hydroxyethyl, or adjacent two groupsof R₃ to R₇ form, taken together, methylenedioxy; and each of R₈ to R₁₉,if present, is selected from the group consisting of hydrido, fluoro,chloro, bromo, methyl, ethyl, n-propyl, isopropyl, acetyl, propionyl,methoxy, ethoxy, iso-propyloxy, n-propyloxy and formyl; or apharmaceutically-acceptable salt thereof.
 4. A compound according toclaim 1, which is represented by the following Formula II:

wherein Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)-sulfonyl, (N-alkylamino)sulfonyl, or alkylthio; Zrepresents oxygen or sulfur atom; R₁ and R₂ are selected independentlyfrom lower alkyl radicals; and each of R₃ to R₇, if present, isindependently selected from hydrido, halo, alkyl, haloalkyl, alkoxy,haloalkoxy, acyl, nitro, amino, N-alkylamino, N,N-dialkylamino,N-acylamino, N-(haloacyl)amino, formyl, cyano, azido, hydroxy,alkylthio, alkylsulfonyl, phenyl, alkoxyalkyl and hydroxyalkyl, or twoadjacent groups of R₃ and R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.
 5. A compound according toclaim 4, in which Y is selected from (lower alkyl)sulfonyl,aminosulfonyl, (lower alkyl)sulfinyl, (lower N-acylamino)sulfonyl,(lower N-alkylamino)sulfonyl, and (lower alkyl)thio; Z is selected fromoxygen and sulfur atom; R₁ and R₂ are independently selected from methyland ethyl radical; and wherein each of R₃ to R₇, if present, isindependently selected from hydrido, halo, lower alkyl, lower haloalkyl,lower alkoxy, lower haloalkoxy, lower acyl, nitro, amino, lowerN-alkylamino, lower N,N-dialkylamino, lower N-acylamino, (lowerhaloacyl)amino, formyl, cyano, azido, hydroxy, lower alkylthio, loweralkylsulfonyl, phenyl, lower alkoxyalkyl and lower hydroxyalkyl, or twoadjacent groups of R₃ to R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.
 6. A compound according toclaim 5, in which Y is selected from methylsulfonyl, aminosulfonyl,methylsulfinyl, (N-acetylamino)sulfonyl, (N-propionylamino)sulfonyl,(N-butyrylamino)sulfonyl, (N-methylanino)sulfonyl,(N-ethylamino)sulfonyl, and methylthio; Z is selected from oxygen andsulfur atom; R₁ and R₂ are independently selected from methyl and ethylradical; and each of R₃ to R₇, if present, is independently selectedfrom hydrido, fluoro, chloro, bromo, methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl,fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl,2,2,2-trifluoroethyl, methoxy, trifluoromethoxy, difluoromethoxy,fluoromethoxy, acetyl, propionyl, n-butanoyl, iso-butanoyl, n-pentanoyl,nitro, amino, N,N-dimethylamino, N-acetylamino, N-propionylamino,formyl, hydroxy, methylthio, ethylthio, n-propylthio, methylsulfonyl,ethylsulfonyl, n-propylsulfonyl, phenyl, hydroxymethyl, 1-hydroxyethyland 2-hydroxyethyl, or adjacent two groups of R₃ to R₇ form, takentogether, methylenedioxy; or a pharmaceutically-acceptable salt thereof.7. A compound according to claim 6, which is selected from the followinggroup of specific compounds:2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-4-(2-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluoro-4-phenylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-5-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Chloro-3-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2,4-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Dichlorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Bromophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Bromophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-ethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-n-propylphenyl)-3(2H)-furanone;2,2-Dimethyl-4-(3-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluoro-4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-iso-propylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-n-butylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-t-butylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-fluoro-2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(5-fluoro-2-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluoro-4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2,4-Dimethoxyphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Dimethoxyphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3,4-methylenedioxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3,4-dimethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluoro-4-hydroxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(methylthio)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(ethylthio)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4,5-di-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(ethylsulfonyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{3-(fluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(fluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-(Difluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-(Difluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-Acetyl-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{3,5-di-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-Chloro-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-nitrophenyl)-3(2H)-furanone;4-(3-Aminophenyl)-2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(N,N-dimethylamino)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-formylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-(Acetylamino)phenyl}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetylphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Biphenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-[4-(1-hydroxyethyl)phenyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-[4-(1-hydroxymethyl)phenyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3,5-difluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3-Chloro-5-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(4-t-Butylphenyl)-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-fluorophenyl)-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfinyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-{3-Acetyl-5-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(4-nitrophenyl}-3(2H)-furanone;2,2-Dimethyl-4-(4-methoxyphenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylthio)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3-chloro-5-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,4-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-{3-chloro-5-(trifluoromethyl)phenyl}-2,2-dimethyl3(2H)-furanone;4-{3-Acetyl-5-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl3(2H)-furanone;4-{4-Acetyl-5-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-methylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,4-dimethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(2,4-dimethoxyphenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,4-dimethoxyphenyl)-2,2-dimethyl-3(2H)-furanone;4-(3-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(3-Acetyl-5-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(3-Acetyl-4-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(3-Acetyl-4-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(3-Acetyl-5-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3-chloro-4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-methoxyphenyl)-3(2H)-furanone;4-(4-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(4-Acetyl-3-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(4-Acetyl-3-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-(4-Acetyl-3-bromophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;4-{4-(Acetylamino)phenyl}-5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-methylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-methylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{3,4-(methylenedioxy)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(methylthio)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-fluoro-4-phenylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(4-bromophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-iso-propyl-2-methoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-iso-propylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(ethylthio)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-methoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(4-n-butylphenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,4,5-trimethoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-hydroxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-fluoro-3-methoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3,5-dimethyl-4-methoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-ethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-phenylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;4-(3-Aminophenyl)-5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-nitrophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(5-fluoro-2-methylphenyl)-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;2-Ethyl-4-(4-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(2-fluorophenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-3-chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-3-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-Acetyl-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-5-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(4-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;4-(3-Acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Acetyl-4-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Acetyl-4-chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-(Acetylamino)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-4-{3,4-(methylenedioxy)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-Chloro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;4-{5-Chloro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)-phenyl}-3(2H)-furanone;2-Ethyl-4-{5-fluoro-3-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(4-ethylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-fluoro-4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(5-fluoro-4-iso-propylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-iso-propylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-t-Butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(4-n-propylphenyl)-3(2H)-furanone;4-(4-n-Butylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Dimethylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Aminophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-(Difluoromethyl)phenyl}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-{4-(fluoromethyl)phenyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Chlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethoxy)phenyl}-3(2H)-furanone;4-(4-Chloro-3-fluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(4-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(5-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,4-Dimethoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Dimethoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(5-fluoro-2-methylphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-fluoro-4-methoxyphenyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Dichlorophenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3,5-Dimethyl-4-methoxyphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3,4,5-trimethoxyphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(4-fluorophenyl)-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-fluorophenyl)-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-methylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3-chlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(4-chlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;5-(4-Aminosulfonylphenyl)-2-ethyl-2-methyl-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;5-(4-Aminosulfonylphenyl)-2-ethyl-2-methyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-3(2H)-furanone;5-(4-Aminosulfonylphenyl)-4-{3-chloro-5-(trifluoromethyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,5-difluorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,5-dichlorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(3,4-difluorophenyl)-2-ethyl-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-methoxyphenyl)-2-methyl-3(2H)-furanone;4-(4-Acetylphenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;4-(4-Acetyl-3-chlorophenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;4-(4-Acetyl-3-fluorophenyl)-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;4-{4-Acetyl-4-(trifluoromethyl)phenyl}-5-{4-(aminosulfonyl)phenyl}-2-ethyl-2-methyl-3(2H)-furanone;4-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(4-fluoro-3-methoxyphenyl)-2-methyl-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Diethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-{3-(trifluoromethyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-{3-fluoro-5-(trifluoromethyl)phenyl}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{3-Chloro-5-(trifluoromethyl)phenyl}-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(4-methylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(trifluoromethyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-3-chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-3-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-2-chlorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Acetyl-2-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3,4-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3,5-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(2,5-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-5-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3,4-dimethoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-n-propylphenyl)-3(2H)-furanone;2,2-Diethyl-4-(2,4-difluorophenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-t-Butylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3,4-dimethylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(4-iso-propylphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Acetylphenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-fluorophenyl)-2,2-diethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Diethyl-4-(3-fluoro-4-methoxyphenyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(3-Chloro-4-fluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;2,2-Dimethyl-4-(4-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;2,2-Dimethyl-4-(3-fluorophenyl)-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3thione;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-(2H)-furan-3-thione;5-[4-{(Acetylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-[4-{(Butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-[4-{(N-methylamino)sulfonyl}phenyl]-4-(3-fluorophenyl)-3(2H)-furanone;and2,2-Dimethyl-5-[4-{(N-ethylamino)sulfonyl}phenyl]-4-(3-fluorophenyl)-3(2H)-furanone;or a pharmaceutically-acceptable salt thereof.
 8. A compound accordingto claim 1, which is represented by Formula IV:

wherein X represents halo or alkyl; Y represents alkylsulfonyl,aminosulfonyl, alkylsulfinyl, (N-acylamino)-sulfonyl,(N-alkylamino)sulfonyl, or alkylthio; Z represents oxygen or sulfuratom; and each of R₃ to R₇, if present, is independently selected fromhydrido, halo, alkyl, haloalkyl, alkyloxy, nitro, amino, N-acylamino,acyl, formyl, hydroxyalkyl, phenyl, and cyano, or two adjacent groups ofR₃ to R₇ form, taken together, methylenedioxy; or apharmaceutically-acceptable salt thereof.
 9. A compound according toclaim 8, in which X represents halo or lower alkyl; Y is selected from(lower alkyl)sulfonyl, aminosulfonyl, (lower alkyl)sulfinyl, (lowerN-acylamino)sulfonyl, (lower N-alkylamino)sulfonyl, and (loweralkyl)thio; Z is selected from oxygen and sulfur atom; and each of R₃ toR₇, if present, is independently selected from hydrido, halo, loweralkyl, lower haloalkyl, lower alkyloxy, nitro, amino, and N-(loweracyl)amino; or a pharmaceutically acceptable salt thereof.
 10. Acompound according to claim 9, in which X represents fluoro, chloro,bromo or methyl; Y is selected from methylsulfonyl, ethylsulfonyl,aminosulfonyl, methylsulfinyl, ethylsulfinyl, (N-acetylamino)sulfonyl,(N-propionylamino)sulfonyl, (N-butyrylamino)sulfonyl,(N-methylamino)sulfonyl, (N-ethylamino)sulfonyl, methylthio, andethylthio; Z is selected from oxygen and sulfur atom; and each of R₃ toR₇, if present, is independently selected from hydrido, fluoro, chloro,bromo, methyl, ethyl, iso-propyl, fluoromethyl, difluoromethyl,trifluoromethyl, methoxy, ethoxy, n-propyloxy, iso-propyloxy, n-butoxy,nitro, amino, N-acetylamino, and N-propionylamino; or apharmaceutically-acceptable salt thereof.
 11. A compound according toclaim 10, which is selected from the following group of compounds:2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(4-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,4-Dichlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,4-dichlorophenyl)-2,2-dimethyl-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2,6-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(2,6-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(2-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(2-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{-3-fluoro-4-(methylthio)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-4-(4-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(4-nitrophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-fluorophenyl)-2,2-dimethyl-4-(4-nitrophenyl)-3(2H)-furanone;4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(4-Aminophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(4-Aminophenyl)-5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-3(2H)-furanone;4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-{4-(Acetylamino)phenyl}-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{4-(Acetylamino)phenyl}-5-{4-(aminosulfonyl)-3-fluorophenyl}-2,2-dimethyl-3(2H)-furanone;2-2-Dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-4-(3-methoxyphenyl)-3(2H-furanone;2-2-Dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-4-(3-methoxyphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(2-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(2-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(2-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(2,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,4-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl}-2-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylthio)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfinyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;2,2-Dimethyl-5-{2-fluoro-4-(methylsulfonyl)phenyl}-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-fluorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-bromophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(4-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(4-fluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(2,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3,4-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-methylphenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{3-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-chlorophenyl}-2,2-dimethyl-4-(3-trifluoromethylphenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-2,2-dimethyl-4-(4-fluorophenyl)-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(2,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylthio)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfonyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{2-Chloro-4-(methylsulfinyl)phenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-2-chlorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;2,2-Dimethyl-5-{3-methyl-4-(methylthio)phenyl}-4-phenyl-3(2H)-furanone2,2-Dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-4-phenyl-3(2H)-furanone;2,2-Dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-4-phenyl-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone;2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-fluorophenyl)-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5{-4-(Aminosulfonyl)-3-methylphenyl}-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylthio)phenyl}-3(2H)-furanone4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfinyl)phenyl}-3(2H)-furanone;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-methyl-4-(methylsulfonyl)phenyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)-3-methylphenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-3(2H)-furanone;5-{3-Chloro-4-(N-methylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone5-{3-Chloro-4-(N-ethylaminosulfonyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone5-[4-{(Acetylamino)sulfonyl}-3-chlorophenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-[3-Chloro-4-{(N-n-propionylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;5-[3-Chloro-4-{(N-n-butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-phenyl-3(2H)-furanone;4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylthio)phenyl}-(2H)-furan-3-thion4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfonyl)phenyl}-(2H)-furan-3-thion4-(3-Chlorophenyl)-2,2-dimethyl-5-{3-fluoro-4-(methylsulfinyl)phenyl}-(2H)-furan-3-thion5-{4-(Aminosulfonyl)-3-fluorophenyl}-4-(3-chlorophenyl)-2,2-dimethyl-(2H)-furan-3-thion4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylthio)phenyl}-(2H)-furan-3-thione;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylsulfonyl)phenyl}-(2H)-furan-3-thione;4-(3,5-Difluorophenyl)-2,2-dimethyl-5-{3-fluoro-(4-methylsulfinyl)phenyl}-(2H)-furan-3-thione;and5-{(4-Aminosulfonyl)-3-fluorophenyl}-4-(3,5-difluorophenyl)-2,2-dimethyl-(2H)-furan-3-thione;or a pharmaceutically-acceptable salt thereof.
 12. A compound accordingto claim 1, which is represented by Formula V:

wherein Y represents alkylsulfonyl, aminosulfonyl, alkylsulfinyl,(N-acylamino)sulfonyl, (N-alkylamino)sulfonyl, or alkylthio; Zrepresents oxygen or sulfur atom; wherein R₁ and R₂ are independentlyselected from methyl and ethyl radical; and AR is a substituted ornon-substituted aromatic group of 5 to 10 atoms excluding substituted ornon-substituted phenyl group; or a pharmaceutically-acceptable saltthereof.
 13. A compound according to claim 12, in which Y is selectedfrom (lower alkyl)sulfonyl, aminosulfonyl, and (lowerN-acylamino)sulfonyl; Z is selected from oxygen and sulfur atom; R₁ andR₂ are independently selected from methyl and ethyl radical; and AR isselected from the following specific aromatic groups:

wherein, each of R₈ to R₁₉, if present, is selected from hydrido, halo,lower alkyl, lower acyl, lower haloalkyl, lower alkoxy, formyl, cyano,nitro, amino, azido, and N-acylamino; or a pharmaceutically acceptablesalt thereof.
 14. A compound according to claim 13, in which Y isselected from methylsulfonyl, ethylsulfonyl, aminosulfonyl,(N-acetylamino)sulfonyl, and (N-propionylamino)sulfonyl; Z is selectedfrom oxygen and sulfur atom; R₁ and R₂ are independently selected frommethyl and ethyl radical; and each of R₈ to R₁₉, if present, is selectedfrom hydrido, fluoro, chloro, bromo, methyl, ethyl, iso-propyl, acetyl,n-proionyl, trifluoromethyl, methoxy, ethoxy, and formyl; or apharmaceutically acceptable salt thereof.
 15. A compound according toclaim 14, which is selected from the following group of compounds:2,2-Dimethyl-5-{4-(methylthio)phenyl}-4-(3-thienyl)-3(2H-furanone;2,2-Dimethyl-4-{2-(3-methylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H-furanone;2,2-Dimethyl-4-{2-(5-formylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)furanone;4-(2-Benzo[b]thienyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(1-naphthyl)-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-pyridyl)-3(2H)-furanone;4-(2-Benzo[b]furanyl)-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-naphthyl)-3(2-furanone;2,2-Dimethyl-4-{5-(2-fluorothienyl}-5-{4-(methylsulfonyl)phenyl}-3(2-furanone;2,2-Dimethyl-4-{5-(3-fluorothienyl}-5{-(methylsulfonyl)phenyl}-3(2H-furanone;2,2-Dimethyl-4-{4-(2-fluorothienyl}-5-{4-(methylsulfonyl)phenyl}-3(2-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2-furanone;4-{2-(5-Acetylthienyl)}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(2-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-(3-furanyl)-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{5-(3-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{5-(2-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(2-fluorofuranyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(1-N-ethylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyridyl)-3(2H)-furanone;2,2-Dimethyl-4-{3-(6-methoxypyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{4-(1-N-iso-propylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(5-pyrimidinyl)-3(2H)-furanone;2,2-Dimethyl-4-{3-(6-methylpyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-{2-(5-formyl-4-methylthienyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-4-[2-{5-(1,3-dioxoian)-2-yl}thienyl]-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{2-(5-Bromothienyl)}-2,2-dimethyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2,2-Dimethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazolyl)-3(2-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(2-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(4-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(1-N-methylpyrazolyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(1-N-ethylpyrazolyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-2-methyl-4-(3-thienyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(2-fluorothienyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(2-fluorothienyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(3-fluorothienyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(2-furanyl)-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-(3-furanyl)-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(3-fluorofuranyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{4-(2-fluorofuranyl)}-2-methyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2-ethyl-4-{5-(2-fluorofuranyl)}-2-methyl-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(2-pyridyl)-3(2H)-furanone;2,2-Diethyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyridyl)-3(2H)-furanone;2,2-Diethyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-pyridyl)-3(2H)-furanone;2-Ethyl-2-methyl-4-{4-(1-N-methylpyrazolyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(4-pyrazolyl)-3(2H)-furanone;2-Ethyl-4-{4-(1-N-ethylpyrazoly)}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;2-Ethyl-2-methyl-4-{3-(6-methoxypyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-4-{3-(6-methylpyridyl)}-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(3-thienyl)-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{4-(2-fluorothienyl)}-3(2H)-furanone;2-Ethyl-4-(2-furanyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-(3-furanyl)-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-{5-(3-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-{5-(2-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-4-{4-(2-fluorofuranyl}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2-Benzo[b]thienyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-(2-Benzo[b]furanyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-(2-thienyl)-3(2H)-furanone;2-Ethyl-4-{5-(2-fluorothienyl)}-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;4-{2-(5-Acetylthienyl)}-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(5-methylthienyl)}-3(2H)-furanone;2-Ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-4-{2-(3-methylthienyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-furanyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-furanyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(3-fluorofuranyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(2-fluorofuranyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(2-fluorofuranyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-thienyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-thienyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(2-fluorothienyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(2-fluorothienyl)}-3(2H-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{5-(3-fluorothienyl}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(2-benzo[b]thienyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-4-(2-benzo[b]furanyl)-2,2-dimethyl-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2 dimethyl-4-(2-naphthyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(1-naphthyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(2-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(3-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-pyridyl)-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-methylpyrazolyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-ethylpyrazolyl)}-3(2H)-furanone;5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-{4-(1-N-iso-propylpyrazolyl)}-3(2H)-furanone;and5-{4-(Aminosulfonyl)phenyl}-2,2-dimethyl-4-(4-pyrazolyl)-3(2H)-furanone;or a pharmaceutically-acceptable salt thereof.
 16. A pharmaceuticalcomposition containing a therapeutically-effective amount of a compoundof any one of claims 1-7 and 8-15 for treating an inflammatory disease.17. A pharmaceutical composition containing a therapeutically-effectiveamount of a compound of any one of claims 1-7 and 8-15 for treating aninflammation-associated disease.
 18. A pharmaceutical compositioncontaining a therapeutically-effective amount of a compound of any oneof claims 1-7 and 8-15 for treating a cycloozygenase-2 mediated disease.19. A pharmaceutical composition containing a therapeutically-effectiveamount of a compound of any one of claims 1-7 and 8-15 for treating adisease susceptible to nonsteroidal anti-inflammatory drugs.
 20. Aprocess for the synthesis of 4,5-diaryl-2,2-dimethyl-3-(2H)-furanonecompounds of Formula I, comprising reacting α-bromoisobutyryl cyanidewith 1,2 diarylethanone in the presence of a base in accordance with thefollowing reaction scheme

wherein Y is selected from alkylthio and alkysulfonyl; X is selectedfrom hydrido, halo and alkyl; and AR represents a substituted ornon-substituted aromatic group of 5 to 10 atoms.
 21. A process fortreating a cyclooxygenase-2 mediated disease which comprisesadministering to a person in need thereof a therapeutically effectiveamount of a sulfoxide compound of the Formula VI

wherein X represents halo, hydrido, or alkyl; R₁ and R₂ are selectedindependently from lower alkyl radicals; and AR represents a substitutedor non-substituted aromatic group of 5 to 10 atoms. the sulfoxidecompound being transformed after absorption into the body into thecorresponding sulfone compound of the formula VII.